Variant classification summary

NM_001202543.1:c.*24339G>A

· ·

GRCh37: None · GRCh38: None

Gene: Transcript:

Final call

VUS

Variant details

Gene

Transcript

Protein

gnomAD AF

ClinVar

None

OncoKB

None

Classification rationale

Interpretation summary

Generated evidence synthesis

1

NM_001202543.1:c.*24339G>A is a 3' UTR substitution in an unresolved gene. VariantValidator reports the coordinate is outside the bounds of the reference sequence, precluding gene-level normalization.

2

No population frequency data are available; gnomAD v2.1 and v4.1 returned null results, and gnomAD-Canada shows zero coverage (AC=0, AN=0) at this non-coding position.

3

No ClinVar entries, literature reports, functional studies, cosegregation data, or in silico predictions are available for this variant.

4

No ACMG/AMP pathogenic or benign criteria are met. The variant lacks sufficient evidence for any classification other than Uncertain Significance.

Final determination: Generic ACMG/AMP 2015 fallback rules do not meet benign, likely benign, likely pathogenic, or pathogenic combination thresholds, so the variant is classified as Variant of Uncertain Significance.

Criteria assessment

ACMG/AMP criteria review

Criteria shown when status is available

All criteria require review: For research and educational purposes only.

Criterion	Status	Rationale	Evidence used
PVS1	N/A	NM_001202543.1:c.*24339G>A is a 3' UTR substitution located 24,339 nucleotides downstream of the stop codon. This variant type is not predicted to cause loss of function via any PVS1-eligible null mechanism (nonsense, frameshift, canonical splice, initiation codon, or exon deletion) as defined by the ClinGen SVI PVS1 decision framework (PMC6185798). Additionally, the gene could not be resolved, so loss-of-function as a disease mechanism cannot be established.	pvs1_variant_assessment pvs1_gene_context pvs1_generic_framework
PS1	N/A	PS1 requires the same amino acid change as an established pathogenic variant. This is a 3' UTR variant with no amino acid change; PS1 is not applicable to non-coding substitutions without protein consequence.
PS2	Not met	No de novo observation has been reported for NM_001202543.1:c.*24339G>A. No ClinVar submissions, literature reports, or family study data are available for this variant.
PS3	Not met	No well-established in vitro or in vivo functional studies have been identified for NM_001202543.1:c.*24339G>A. No literature reports, OncoKB entries, or other curated functional evidence are available.
PS4	Not met	No case-control or statistical evidence demonstrates enrichment of NM_001202543.1:c.*24339G>A in affected individuals. No ClinVar submissions, publications, or cohort data are available.
PS5	N/A	PS5 requires a novel missense variant at the same amino acid residue as another pathogenic missense, with very strong supporting evidence. This is a 3' UTR variant with no amino acid change; PS5 is not applicable.
PM1	Not met	No evidence places NM_001202543.1:c.*24339G>A in a mutational hotspot or well-established critical functional domain. The gene is unresolved and no domain mapping is available for this 3' UTR position.
PM2	Not assessed	Population frequency data for NM_001202543.1:c.*24339G>A is unavailable. gnomAD v2.1 and v4.1 returned null results; gnomAD-Canada returned AC=0, AN=0 (zero coverage at this position). Since this is a deep 3' UTR variant, standard gnomAD calling does not cover this region. PM2 cannot be evaluated without population frequency data.
PM5	N/A	PM5 requires a novel missense change at an amino acid residue where a different missense change is pathogenic. NM_001202543.1:c.*24339G>A is a 3' UTR variant with no amino acid change and no protein residue. PM5 candidate harvesting confirmed no eligible comparators.	pm5_candidates
PM6	Not met	No de novo observation with confirmed maternity/paternity has been reported for NM_001202543.1:c.*24339G>A. No literature or clinical submissions document a de novo event.
PP1	Not met	No cosegregation data are available for NM_001202543.1:c.*24339G>A. No family studies, linkage analyses, or segregation reports exist for this variant.
PP2	N/A	PP2 applies to missense variants in genes with a low rate of benign missense variation where missense is a known disease mechanism. NM_001202543.1:c.*24339G>A is a 3' UTR variant, not a missense change; PP2 is not applicable.
PP3	Not met	No in silico prediction tools support a deleterious effect for NM_001202543.1:c.*24339G>A. REVEL and BayesDel are not available for non-coding variants; no REVEL or BayesDel scores were returned. SpliceAI delta scores are null.
PP4	Not met	No specific phenotype or family history data link NM_001202543.1:c.*24339G>A to disease. The gene is unresolved, and no clinical phenotype information is available in any source.
PP5	Not met	No reputable source has classified NM_001202543.1:c.*24339G>A as pathogenic. ClinVar has no entry for this variant, and no literature reports a pathogenic classification.
BA1	Not assessed	BA1 requires an allele frequency >1% in a reference population. Population frequency data for NM_001202543.1:c.*24339G>A is unavailable; gnomAD v2.1 and v4.1 returned null results, and gnomAD-Canada shows zero coverage (AC=0, AN=0). BA1 cannot be evaluated without frequency data.
BS1	Not assessed	BS1 requires an allele frequency >0.3% in a reference population. As with BA1, population frequency data for this 3' UTR variant is unavailable through standard gnomAD resources. BS1 cannot be evaluated.
BS2	Not met	No observation of NM_001202543.1:c.*24339G>A in a healthy adult in the homozygous state, hemizygous state, or in trans with a known pathogenic variant has been reported. No population genotype data are available.
BS3	Not met	No well-established functional studies demonstrate a neutral or benign effect for NM_001202543.1:c.*24339G>A. No in vitro or in vivo functional data are available for this variant.
BS4	Not met	No segregation data demonstrate lack of cosegregation with disease for NM_001202543.1:c.*24339G>A. No family studies are available.
BP1	N/A	BP1 applies to missense variants in genes where a primarily truncating mechanism causes disease. NM_001202543.1:c.*24339G>A is a 3' UTR variant, not a missense change; BP1 is not applicable.
BP2	Not met	No observation of NM_001202543.1:c.*24339G>A in trans with a known pathogenic variant has been reported. No phase-resolved genotype data are available.
BP3	N/A	BP3 applies to in-frame deletions/insertions in non-repeat regions. This variant is a single nucleotide substitution in the 3' UTR.
BP4	Not met	No in silico tools predict a benign or neutral effect for NM_001202543.1:c.*24339G>A. REVEL and BayesDel are unavailable for non-coding variants, and SpliceAI returns null scores. Computational evidence is insufficient to assign BP4.
BP5	Not met	No alternative molecular basis for disease has been identified in a case where NM_001202543.1:c.*24339G>A is present. No clinical context data are available.
BP6	Not met	No reputable source has classified NM_001202543.1:c.*24339G>A as benign. ClinVar has no entry for this variant.
BP7	N/A	BP7 applies to synonymous (silent) variants for which splicing algorithms predict no impact and the nucleotide is not highly conserved. NM_001202543.1:c.*24339G>A is a 3' UTR variant, not a synonymous coding change; BP7 is not applicable.
PM3	N/A	PM3 applies to variants observed in trans with a pathogenic variant in recessive disorders. Gene and disease context are unresolved; this criterion cannot be assessed and is trivial for this case.
PM4	N/A	PM4 applies to protein length changes from in-frame deletions/insertions in non-repeat regions. This variant is a single nucleotide substitution in the 3' UTR.

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