The SERPINA1 NM_001127701.1:c.863A>T (NP_001121173.1:p.(Glu288Val)) missense variant has previously been reported in somatic cancers (COSMIC; COSV63345500, n = 1 time). Based on available guidelines, this variant is considered to be Benign.
Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.
Benign.A benign classification under the recorded framework.
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.SERPINA1 encodes alpha-1 antitrypsin, a serine protease inhibitor made mainly in the liver that helps control enzymes such as elastase, trypsin, and thrombin. Changes in this gene are associated with chronic obstructive pulmonary disease, emphysema, and chronic liver disease. No established role in cancer is indicated.
The recorded framework is Generic ACMG/AMP 2015 with ClinGen SVI recommendations. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
The applied criteria and their strengths are shown as assessed under the stated framework.
Met: the established SERPINA1 PiS allele is the same Glu-to-Val substitution, reported as mature-protein Glu264Val versus precursor Glu288Val here.
Met at supporting strength: REVEL 0.692 exceeds the generic PP3 supporting threshold of 0.644 for this missense variant.
Met: Amish gnomAD v4.1 frequency is 12.61% (115/912 alleles), exceeding the generic BA1 >=5% threshold despite lower all-comers frequency.
Benign: BA1 stand-alone benign is met; PS1 strong plus PP3 supporting does not satisfy a pathogenic combination under generic ACMG/AMP rules.
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1: 58,691 / 1,614,182 alleles. Recorded AF 0.0363596. Recorded homozygote count 1342.
This variant is present in gnomAD v2.1 (AF= 0.0233536; MAF= 2.33536%, 6606/282868 alleles, homozygotes = 143) and has highest observed frequency in the European (non-Finnish) population (AF= 0.0366786; MAF= 3.66786%, 4738/129176 alleles, homozygotes = 117); grpmax FAF= 0.0356068.
This variant is present in gnomAD-Canada v1.0 (AF= 0.035237267890107504, 649/18418 alleles, homozygotes = 16).
Recorded REVEL score: 0.692. Refer to the recorded PP3/BP4 rationale for interpretation.
23 Pathogenic · 1 Uncertain significance · 1 Pathogenic, low penetrance · 1 other · 1 pathogenic. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
No standalone functional evidence summary is recorded in evidence_summary.functional.
This variant has previously been reported in somatic cancers (COSMIC; COSV63345500, n = 1 times).
This variant does not lie in a statistically significant hotspot.
ACMG/AMP criteria under Generic ACMG/AMP 2015 with ClinGen SVI recommendations, with the data and sources behind each one.
28 criteria with recorded statuses: 3 met · 4 not met · 16 not assessed · 5 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
No VCEP covers SERPINA1 in this case, so the generic ACMG/AMP rules govern.
The exact variant is common in gnomAD, but that population frequency does not replace the variant-specific affected-versus-control comparison required for PS4.
ClinVar's laboratory and aggregate assertions do not satisfy the exact-variant expert-panel requirement applied here for PP5 or BP6.
No VCEP covers SERPINA1, so generic ACMG/AMP rules with the supplied ClinGen SVI thresholds govern.
The variant is missense, so PP3 and BP4 use exactly one computational path: REVEL; SpliceAI is not used for either criterion.
REVEL 0.692 meets the generic PP3 supporting threshold of >= 0.644 but does not meet the generic BP4 supporting threshold of <= 0.29.
No criteria match.
The queried variant is NP_001121173.1:p.(Glu288Val), corresponding to the mature-protein numbering p.Glu264Val used for the established SERPINA1 PiS allele. Matamala et al. explicitly introduced the S (Glu264Val) change into SERPINA1 expression constructs and described S among the pathological SERPINA1 variants associated with alpha-1-antitrypsin deficiency. This is the same amino-acid substitution, not merely an alternate change at the same residue; no splice-specific interpretation is needed for this missense substitution.
Same amino acid change as a previously established pathogenic variant regardless of nucleotide change. ... Caveat: Beware of changes that impact splicing rather than at the amino acid/protein level.
The variant is NM_001127701.1:c.863A>T, p.(Glu288Val), a missense SNV. Under the generic missense path, PP3 is evaluated with REVEL only; the SpliceAI score is not used for a missense PP3/BP4 decision. The REVEL score is 0.692, which meets the supplied generic ClinGen SVI supporting PP3 threshold of >= 0.644 (Pejaver et al. 2022, PMID:36413997). Therefore PP3 is met at supporting strength. BayesDel is not used because no generic ACMG-strength calibration is established for it, and the SpliceAI prediction is not double-counted on the missense path.
PP3 (supporting): >= 0.644 — ClinGen SVI REVEL calibration (Pejaver et al. 2022, Am J Hum Genet) (PMID:36413997)
BA1 is met because the variant has an observed allele frequency of 0.126096 (115/912 alleles; 9 homozygotes) in the Amish population in gnomAD v4.1, exceeding the generic stand-alone threshold of >=0.05. The all-comers gnomAD v4.1 frequency is 0.0363596 and grpmax FAF is 0.0443425, both below 5%, so the BA1 call depends on the documented Amish ancestry-specific frequency; the small ancestry sample and the known reduced-penetrance alpha-1-antitrypsin phenotype warrant human review. The variant is an SNV, so the indel calling caveat does not apply.
Allele frequency is above 5% in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium.
PM2 is not met because the variant is common in population controls rather than absent or extremely rare. The preferred non-cancer subsets show AF 0.0227311 (5386/236944 alleles; 119 homozygotes) in gnomAD v2.1 non-cancer exomes and AF 0.0286054 (4232/147944 alleles; 102 homozygotes) in gnomAD v3.1 non-cancer genomes; the default all-comers datasets are also high at AF 0.0233536 in gnomAD v2.1 and AF 0.0363596 in gnomAD v4.1. These values all greatly exceed the generic PM2 supporting threshold of <=0.0001.
Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium.
PP5 is not met because the available exact-variant ClinVar record has no expert-panel submission and is reported as criteria-provided laboratory submissions and aggregate classifications. The record's 23 laboratory Pathogenic submissions are not a reputable source meeting the required independent-evaluation exception, and no paper reviewed in this group provides a qualifying reputable exact-variant pathogenic report whose evidence is unavailable for independent evaluation.
Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation.
The variant is NM_001127701.1:c.863A>T, p.(Glu288Val), a missense SNV. Under the generic missense path, BP4 is evaluated with REVEL only; the SpliceAI score is not used to establish BP4 for a missense variant. The REVEL score is 0.692, which is above the supplied generic BP4 supporting threshold of <= 0.29 (Pejaver et al. 2022, PMID:36413997), so BP4 is not met. The score is not a benign BP4 result, and the SpliceAI max delta score of 0.688 cannot substitute for the applicable REVEL path. BayesDel is not used because no generic ACMG-strength calibration is established for it.
BP4 (supporting): <= 0.29 — ClinGen SVI REVEL calibration (Pejaver et al. 2022, Am J Hum Genet) (PMID:36413997)
BP6 is not met because the exact-variant ClinVar record contains no expert-panel benign or likely-benign classification. Instead, it reports an overall Pathogenic classification with laboratory submissions and no expert-panel submissions; no reviewed source provides a qualifying reputable exact-variant benign report whose evidence is unavailable for independent evaluation.
Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.
PS2 cannot be assessed because the available evidence does not document a proband-level de novo observation, disease phenotype, absence of family history, or confirmed maternity and paternity. In particular, no parental testing results or parentage confirmation are available to establish that the variant arose de novo.
De novo (both maternity and paternity confirmed) in a patient with the disease and no family history.
No variant-specific, validated in vitro or in vivo functional assay for SERPINA1 NM_001127701.1:c.863A>T (p.Glu288Val) was identified in the available evidence. PMID:29232161 experimentally characterized other SERPINA1 missense variants but did not mention this variant; PMID:26141072 and PMID:6602622 evaluated PiSZ clinical phenotypes rather than the queried substitution in a functional assay. Therefore the evidence does not establish PS3 at any strength, but the criterion is not assessed rather than considered not met because absence of an identified assay is not evidence against a damaging effect.
Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product.
The governing PS4 rule requires a significantly increased prevalence in affected individuals versus controls; the supplied literature contains no variant-specific case-control counts, affected-versus-unaffected comparison, odds ratio, relative risk, or confidence interval for SERPINA1 c.863A>T (p.Glu288Val). The papers indexed for PS4 were verified through their available extracts: PMID:26141072 and PMID:6602622 study PiSZ/PiSZ-related cohorts but do not mention this exact variant, and literature_pass.json has no packet.ai_classified_papers entries. Therefore the PS4 threshold cannot be evaluated. The exact variant is common in gnomAD, but population frequency alone is not a case-control comparison and does not supply the required affected-case prevalence.
The prevalence of the variant in affected individuals is significantly increased compared to the prevalence in controls. ... Relative risk (RR) or odds ratio (OR), as obtained from case-control studies, is >5.0 and the confidence interval around the estimate of RR or OR does not include 1.0.
No VCEP specification or authoritative domain table is available for SERPINA1. The case evidence reports no statistically significant Cancer Hotspots result for SERPINA1 E288, and the supplied evidence does not establish that residue 288 lies in a generic ACMG critical functional domain that lacks benign variation. Therefore PM1 cannot be adjudicated from the available evidence.
Located in a mutational hot spot and/or critical and well-established functional domain (e.g. active site of an enzyme) without benign variation.
PM3 cannot be assessed. The available evidence does not document an affected proband with NM_001127701.1:c.863A>T (p.Glu288Val) in trans with a pathogenic variant, and no parental or offspring testing establishes phase. ClinVar classifications and population observations do not establish trans phase or provide an affected-proband allelic observation.
For recessive disorders, detected in trans with a pathogenic variant ... Note: This requires testing of parents (or offspring) to determine phase.
The available evidence confirms the same Glu-to-Val substitution as the established PiS allele, which supports PS1, but does not identify a different pathogenic missense substitution at residue 288. The PM5 candidate artifact contains no comparator candidates and explicitly does not confirm classic same-residue PM5 semantics. A different pathogenic missense change at Glu288 is therefore not established.
Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before. ... Caveat: Beware of changes that impact splicing rather than at the amino acid/protein level.
PM6 cannot be assessed because the available evidence does not document an assumed de novo variant in the proband. There are no reported parental genotypes, family-history details, or case-level data establishing de novo occurrence without maternity and paternity confirmation.
Assumed de novo, but without confirmation of paternity and maternity.
PP1 cannot be assessed because no affected family members, informative meioses, genotype results, or co-segregation observations are documented. The available literature extracts concern general SERPINA1 disease or unrelated variants and do not provide variant-specific family segregation for c.863A>T (p.Glu288Val).
Co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease.
The case evidence does not provide a gene-wide estimate establishing both a low rate of benign missense variation and missense variants as a common disease mechanism for SERPINA1. A high population frequency for this particular variant and descriptions of individual SERPINA1 missense alleles cannot by themselves establish both PP2 requirements.
Missense variant in a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
No patient-specific phenotype, family history, or clinical presentation for the queried case is supplied in the evidence bundle. General SERPINA1 PiSZ cohort descriptions in PMID:26141072 and PMID:6602622 are not specific to this exact variant and cannot establish that this patient's phenotype is highly specific for a disease with a single genetic etiology. Accordingly, PP4 cannot be adjudicated.
Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology.
BS1 is not assessed. The observed frequency is high (gnomAD v4.1 overall AF 0.0363596; European non-Finnish AF 0.0446621; Amish AF 0.126096), but the prompt requires a maximum-credible-allele-frequency assessment before using the 1% default. No disorder prevalence, penetrance, allelic heterogeneity, or other inputs sufficient for a Whiffin et al. (2017) maximum-credible-frequency calculation are available here. Alpha-1-antitrypsin deficiency is represented as reduced penetrance/late-onset in the case evidence, so the default 1% threshold alone is not sufficient.
Allele frequency is greater than expected for disorder.
No variant-specific, validated in vitro or in vivo functional assay for SERPINA1 NM_001127701.1:c.863A>T (p.Glu288Val) was identified in the available evidence. PMID:29232161 experimentally characterized other SERPINA1 missense variants but did not mention this variant; PMID:26141072 and PMID:6602622 evaluated PiSZ clinical phenotypes rather than demonstrating preserved function of the queried substitution. Therefore the evidence does not establish BS3 at any strength, but the criterion is not assessed rather than considered not met because absence of an identified assay is not evidence for a benign functional effect.
Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing.
BS4 cannot be assessed because no family containing affected members with documented negative variant testing is described. There is therefore no variant-specific non-segregation observation to distinguish lack of segregation from phenocopy, variable expressivity, incomplete ascertainment, or another cause of an apparently discordant phenotype.
Lack of segregation in affected members of a family.
The case evidence does not establish that SERPINA1-related disease is caused primarily by truncating variants. It documents missense disease-associated SERPINA1 alleles, including PiS, but that observation alone is not a complete gene-level comparison of truncating versus missense disease mechanisms. BP1 therefore cannot be adjudicated definitively from the available evidence.
Missense variant in a gene for which primarily truncating variants are known to cause disease.
BP2 cannot be assessed. The available evidence does not document this variant in trans with a pathogenic variant in a fully penetrant dominant disorder, or in cis with a pathogenic variant in any inheritance pattern. No proband-level phase testing, family genotypes, or variant-specific cis/trans observation is available.
Observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.
No evidence in the supplied case materials documents that SERPINA1 c.863A>T was found in a case with an alternate molecular basis for disease. The available PiSZ cohort papers do not mention this exact variant, and the ClinVar record supplies classifications and conditions rather than a documented alternate molecular diagnosis in a specific case. BP5 therefore cannot be adjudicated from the available evidence.
Variant found in a case with an alternate molecular basis for disease.
PVS1 (ClinGen SVI PVS1 recommendations, PMC6185798, pvs1_generic_framework) applies only to null variant classes — nonsense, frameshift, canonical ±1/2 splice-consensus, translation-initiation-codon loss, and stop-loss variants — each expected to trigger nonsense-mediated decay or otherwise abolish normal protein function. NM_001127701.1:c.863A>T in SERPINA1 is a missense substitution predicted to produce NP_001121173.1:p.(Glu288Val). As a result, no null-variant mechanism (nonsense-mediated decay, truncation, or canonical splice disruption) is triggered by this variant class, so PVS1's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PVS1 for SERPINA1, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_null_variant_class
PM4 (Richards et al. 2015, PMID:25741868) applies to protein length changes: in-frame insertions/deletions in a non-repetitive region, or stop-loss variants that extend the protein past the reference stop codon. NM_001127701.1:c.863A>T in SERPINA1 is a missense substitution predicted to produce NP_001121173.1:p.(Glu288Val). As a result, no change in protein length occurs, so there is nothing for this criterion to evaluate, so PM4's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PM4 for SERPINA1, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_stop_loss_or_nonrepeat_indel
BS2 is not applicable because the governing definition requires observation in a healthy adult with full penetrance expected at an early age. The available population data show 1342 homozygotes in gnomAD v4.1, 143 homozygotes in gnomAD v2.1, 119 homozygotes in gnomAD v2.1 non-cancer exomes, and 102 homozygotes in gnomAD v3.1 non-cancer genomes, but gnomAD population records do not establish that these individuals are phenotypically healthy adults or that this late-onset/reduced-penetrance alpha-1-antitrypsin phenotype should be fully penetrant early in life.
Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age.
BP3 (Richards et al. 2015, PMID:25741868) applies to in-frame insertions/deletions located in a repetitive region without a known function. NM_001127701.1:c.863A>T in SERPINA1 is a missense substitution predicted to produce NP_001121173.1:p.(Glu288Val). As a result, the variant does not alter protein length within a repeat region, so there is nothing for this criterion to evaluate, so BP3's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP3 for SERPINA1, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_repeat_region_indel
BP7 (Richards et al. 2015, PMID:25741868) is defined for a synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence and the nucleotide is not highly conserved. NM_001127701.1:c.863A>T in SERPINA1 is a missense substitution predicted to produce NP_001121173.1:p.(Glu288Val). As a result, the encoded protein sequence is altered, so the criterion's silent-variant premise does not hold regardless of any splicing prediction, so BP7's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP7 for SERPINA1, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_synonymous
Every interpreted variant in SERPINA1, mapped onto the exon structure of NM_001127701.1. Select a row to find it on the plot.
| Protein | Location | Classification | Link |
|---|
| Amish115 / 912 | 0.139 hom |
| European (non-Finnish)52701 / 1,179,994 | 0.0451229 hom |
| Admixed American2287 / 60,016 | 0.03854 hom |
| Remaining individuals2054 / 62,504 | 0.03339 hom |
| Ashkenazi Jewish402 / 29,606 | 0.0144 hom |
| European (Finnish)537 / 64,046 | 0.00845 hom |
| African/African American580 / 75,070 | 0.00772 hom |
| Middle Eastern7 / 6,062 | 0.0012 |
| South Asian6 / 91,086 | 6.6e-05 |
| East Asian2 / 44,886 | 4.5e-05 |
| European (non-Finnish)4738 / 129,176 | 0.037117 hom |
| Remaining individuals236 / 7,222 | 0.0333 hom |
| Admixed American1074 / 35,440 | 0.0318 hom |
| Ashkenazi Jewish144 / 10,370 | 0.0143 hom |
| European (Finnish)210 / 25,122 | 0.00841 hom |
| African/African American203 / 24,968 | 0.00811 hom |
| East Asian1 / 19,954 | 5e-05 |
This variant is present in gnomAD v4.1 (AF= 0.0363596; MAF= 3.63596%, 58691/1614182 alleles, homozygotes = 1342) and has highest observed frequency in the Amish population (AF= 0.126096; MAF= 12.60965%, 115/912 alleles, homozygotes = 9); grpmax FAF= 0.0443425.
This variant is present in gnomAD v2.1 (AF= 0.0233536; MAF= 2.33536%, 6606/282868 alleles, homozygotes = 143) and has highest observed frequency in the European (non-Finnish) population (AF= 0.0366786; MAF= 3.66786%, 4738/129176 alleles, homozygotes = 117); grpmax FAF= 0.0356068.
This variant is present in gnomAD-Canada v1.0 (AF= 0.035237267890107504, 649/18418 alleles, homozygotes = 16).
The variant is NM_001127701.1:c.863A>T, p.(Glu288Val), a missense SNV. Under the generic missense path, PP3 is evaluated with REVEL only; the SpliceAI score is not used for a missense PP3/BP4 decision. The REVEL score is 0.692, which meets the supplied generic ClinGen SVI supporting PP3 threshold of >= 0.644 (Pejaver et al. 2022, PMID:36413997). Therefore PP3 is met at supporting strength. BayesDel is not used because no generic ACMG-strength calibration is established for it, and the SpliceAI prediction is not double-counted on the missense path.
PP3 (supporting): >= 0.644 — ClinGen SVI REVEL calibration (Pejaver et al. 2022, Am J Hum Genet) (PMID:36413997)
The variant is NM_001127701.1:c.863A>T, p.(Glu288Val), a missense SNV. Under the generic missense path, BP4 is evaluated with REVEL only; the SpliceAI score is not used to establish BP4 for a missense variant. The REVEL score is 0.692, which is above the supplied generic BP4 supporting threshold of <= 0.29 (Pejaver et al. 2022, PMID:36413997), so BP4 is not met. The score is not a benign BP4 result, and the SpliceAI max delta score of 0.688 cannot substitute for the applicable REVEL path. BayesDel is not used because no generic ACMG-strength calibration is established for it.
BP4 (supporting): <= 0.29 — ClinGen SVI REVEL calibration (Pejaver et al. 2022, Am J Hum Genet) (PMID:36413997)
BP7 (Richards et al. 2015, PMID:25741868) is defined for a synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence and the nucleotide is not highly conserved. NM_001127701.1:c.863A>T in SERPINA1 is a missense substitution predicted to produce NP_001121173.1:p.(Glu288Val). As a result, the encoded protein sequence is altered, so the criterion's silent-variant premise does not hold regardless of any splicing prediction, so BP7's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP7 for SERPINA1, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_synonymous
SpliceAI predicts possible splice impact for this variant (max delta score = 0.69). REVEL score = 0.692. BayesDel score = 0.0191118.
10 paper records listed. 1 cited in the classification.
This technique allows the characterization of about 30 normal and pathological variants (e.g. M, I, F, S, and Z). ... In the case of PiSDonosti variant, two expression vectors were generated: one only containing the Donosti substitution (Ser14Phe) and other containing both S (Glu264Val) and Donosti (Ser14Phe) changes.
Location Introduction, lines 95-98; Expression plasmids and DNA transfection, lines 208-219
Context SERPINA1 variant characterization using site-directed mutagenesis, transient HEK293T expression, protein secretion/polymerization assays, elastase inhibition, and clinical variant descriptions.
The S allele leads to a milder deficiency, and there has been considerable debate about whether heterozygous PiSZ patients are at increased risk of lung disease, largely due to the confounding factor of acquisition bias in some prior work.
Introduction, paragraph 1
Next to type Z, type SZ of the less unusual phenotypes has the lowest serum AT concentration (30-40% of normal)
Introduction; Results and Discussion
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
This variant is present in gnomAD v4.1 (AF= 0.0363596; MAF= 3.63596%, 58691/1614182 alleles, homozygotes = 1342) and has highest observed frequency in the Amish population (AF= 0.126096; MAF= 12.60965%, 115/912 alleles, homozygotes = 9); grpmax FAF= 0.0443425.
This variant is present in gnomAD v2.1 (AF= 0.0233536; MAF= 2.33536%, 6606/282868 alleles, homozygotes = 143) and has highest observed frequency in the European (non-Finnish) population (AF= 0.0366786; MAF= 3.66786%, 4738/129176 alleles, homozygotes = 117); grpmax FAF= 0.0356068.
This variant is present in gnomAD-Canada v1.0 (AF= 0.035237267890107504, 649/18418 alleles, homozygotes = 16).
This variant has been reported in ClinVar as Pathogenic (23 clinical laboratories) and as Uncertain significance (1 clinical laboratory) and as Pathogenic, low penetrance (1 clinical laboratory) and as other (1 clinical laboratory) and as pathogenic (1 clinical laboratory). (ClinVarID = 17969)
SpliceAI predicts possible splice impact for this variant (max delta score = 0.69). REVEL score = 0.692. BayesDel score = 0.0191118.
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV63345500, n = 1 times).
This variant does not lie in a statistically significant hotspot.