NM_001202543.1:c.*25175G>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

The NM_001202543.1:c.*25175G>A variant could not be assigned to a validated gene, genomic coordinate, or protein consequence, so somatic cancer and germline disease database observations were not established.

Population frequency could not be evaluated because a validated genomic representation was not available for gnomAD-based review.

No published functional evidence establishing either a damaging or benign effect was identified, and gene-level loss-of-function context remained unresolved for PVS1 consideration.

SpliceAI, REVEL, and BayesDel results were not available for this variant representation, so computational evidence could not support either PP3 or BP4.

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	Not assessed	This variant description does not have a validated gene assignment or transcript-bounded consequence, and germline loss-of-function disease mechanism could not be established for PVS1 use. Available evidence does not support applying generic PVS1 at this time.	pvs1_gene_context pvs1_variant_assessment pvs1_generic_framework
PS1	N/A	This submitted variant is described in the 3' untranslated region and does not define an amino acid substitution, so same-amino-acid-change evidence under PS1 is not applicable.
PS2	Not assessed	No confirmed de novo data were identified for this variant, so PS2 is not assessed.
PS3	Not assessed	No published functional study establishing a damaging effect for this variant was identified, so PS3 is not assessed.
PS4	Not assessed	Case-control or prevalence data showing enrichment in affected individuals were not identified, so PS4 is not assessed.
PM1	N/A	This submitted variant is not a protein-altering missense change with an established critical residue or functional domain, so PM1 is not applicable.
PM2	Not assessed	Population frequency could not be established because no validated genomic coordinates were available for gnomAD-based review, so PM2 is not assessed.
PM3	Not assessed	No allelic-phase or recessive case evidence was identified for this variant, so PM3 is not assessed.
PM4	N/A	This variant is not an in-frame protein length change, so PM4 is not applicable.
PM5	N/A	This submitted variant does not define a missense residue change, and same-residue missense comparator logic could not be applied. PM5 is not applicable.	pm5_candidates
PM6	Not assessed	No assumed de novo evidence without full parental confirmation was identified for this variant, so PM6 is not assessed.
PP1	Not assessed	No segregation data were identified for this variant, so PP1 is not assessed.
PP2	N/A	This submitted variant is not a missense change, so PP2 is not applicable.
PP3	Not assessed	Computational evidence could not be established because SpliceAI, REVEL, and BayesDel results were not available for a validated genomic representation of this variant. PP3 is not assessed.
PP4	Not assessed	No phenotype-specific evidence linking this variant to a highly specific monogenic presentation was identified, so PP4 is not assessed.
PP5	Not assessed	No established pathogenic assertion from a qualifying external source was identified for this variant, so PP5 is not assessed.
BA1	Not assessed	A population frequency high enough for BA1 could not be evaluated because no validated genomic coordinates were available. BA1 is not assessed.
BS1	Not assessed	Population frequency relative to a benign threshold could not be evaluated because no validated genomic coordinates were available. BS1 is not assessed.
BS2	Not assessed	No evidence showing this variant in healthy individuals at a frequency inconsistent with disease was identified, so BS2 is not assessed.
BS3	Not assessed	No published functional study showing no damaging effect for this variant was identified, so BS3 is not assessed.
BS4	Not assessed	No non-segregation data were identified for this variant, so BS4 is not assessed.
BP1	N/A	This submitted variant is not a missense change, so BP1 is not applicable.
BP2	Not assessed	No phase data showing this variant with another pathogenic variant in a configuration supporting BP2 were identified, so BP2 is not assessed.
BP3	N/A	This variant is not an in-frame change in a repetitive region without known function, so BP3 is not applicable.
BP4	Not assessed	Computational evidence supporting no impact was not available because SpliceAI, REVEL, and BayesDel results were not established for a validated genomic representation of this variant. BP4 is not assessed.
BP5	Not assessed	No evidence was identified showing that an alternate molecular cause fully explains the phenotype while this variant is present, so BP5 is not assessed.
BP6	Not assessed	No qualifying external benign assertion was identified for this variant, so BP6 is not assessed.
BP7	N/A	BP7 applies to synonymous or certain intronic variants without predicted splice impact. This submitted 3' untranslated region variant does not meet that criterion definition, so BP7 is not applicable.

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