Variant classification summary

NM_001202543.1:c.*31777C>T

· ·

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

All three requested criteria are not applicable because the submitted variant is a 3' UTR single-nucleotide substitution, whereas PVS1, PM4, and BP3 each require different variant classes explicitly named in their governing definitions.

2

None of PS2, PM6, PP1, or BS4 can be assessed from the available record because proband, parental, pedigree, phenotype, and segregation data are absent, and variant normalization is unresolved.

Final determination: Under the generic ACMG/AMP 2015 fallback, no applied criteria satisfy a pathogenic, likely pathogenic, benign, or likely benign combination, so the variant is classified as VUS.

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
PVS1	N/A	Not applicable: c.*31777C>T is a 3' UTR SNV, not one of the null-variant types named by the PVS1 rule.
PS1	N/A	Not applicable: c.*31777C>T is a downstream-of-stop coordinate, not an amino-acid-changing missense variant eligible for same-amino-acid comparison.
PS2	Not assessed	Not assessed: no proband, family-history, or confirmed maternity-and-paternity results are available to establish a de novo occurrence.
PS3	Not assessed	Not assessed: no variant-specific validated functional assay evidence was available, and normalization failed because the coordinate was outside the reference-sequence bounds.
PS4	Not assessed	Not assessed: no variant-specific case-control prevalence, odds ratio, relative risk, or confidence interval is available for comparison with the PS4 rule.
PM1	N/A	Not applicable: c.*31777C>T lies downstream of the coding sequence, so no codon, protein residue, hotspot, or functional-domain location is available.
PM2	Not assessed	Not assessed: no gnomAD allele frequency is available to compare with the generic PM2 threshold of <=0.0001.
PM3	Not assessed	Not assessed: no gene, inheritance mode, pathogenic partner, affected-proband observation, or parental/offspring phase testing is available.
PM4	N/A	Not applicable: c.*31777C>T is a 3' UTR SNV with no established protein-length change, not an in-frame indel or stop-loss variant.
PM5	N/A	Not applicable: c.*31777C>T is downstream of the coding sequence and specifies no amino-acid residue for alternate-pathogenic-change comparison.
PM6	Not assessed	Not assessed: no patient-level de novo observation or parental testing is documented for an assumed de novo classification.
PP1	Not assessed	Not assessed: no affected relatives, segregation results, informative meioses, or definitive gene-disease relationship are documented.
PP2	N/A	Not applicable: c.*31777C>T is not a missense variant, and the case provides no gene for evaluating missense constraint or disease mechanism.
PP3	N/A	Not applicable: the 3' UTR variant c.*31777C>T is outside the generic PP3 missense and splice-region/intronic computational scope.
PP4	Not assessed	Not assessed: no patient phenotype or family history is available to determine whether the presentation is highly specific for a single-gene disease.
PP5	Not assessed	Not assessed: no exact-variant ClinVar expert-panel Pathogenic or Likely pathogenic classification is available for this unresolved variant.
BA1	Not assessed	Not assessed: no gnomAD allele frequency is available to compare with the generic BA1 threshold of >=0.05.
BS1	Not assessed	Not assessed: no gnomAD allele frequency is available to compare with the generic BS1 threshold of >=0.01.
BS2	Not assessed	Not assessed: no healthy-adult genotype observation is available for the required homozygous, heterozygous, or hemizygous assessment.
BS3	Not assessed	Not assessed: no variant-specific validated functional assay evidence was available, and normalization failed because the coordinate was outside the reference-sequence bounds.
BS4	Not assessed	Not assessed: no affected-family genotypes or phenotype/genotype discordance are documented to demonstrate lack of segregation.
BP1	N/A	Not applicable: c.*31777C>T is not a missense variant, and the case provides no gene for assessing whether truncating variants primarily cause disease.
BP2	Not assessed	Not assessed: no pathogenic partner or phase data show the variant in trans for a fully penetrant dominant disorder or in cis in any inheritance pattern.
BP3	N/A	Not applicable: c.*31777C>T is a 3' UTR SNV, not an in-frame deletion or insertion required for BP3.
BP4	N/A	Not applicable: the 3' UTR variant c.*31777C>T is outside the generic BP4 missense and splice-region/intronic computational scope.
BP5	Not assessed	Not assessed: no case evidence shows an alternate molecular basis for the disease in a patient carrying this unresolved variant.
BP6	Not assessed	Not assessed: no exact-variant ClinVar expert-panel Benign or Likely benign classification is available for this unresolved variant.
BP7	N/A	Not applicable: the 3' UTR variant c.*31777C>T is not a synonymous coding variant within BP7's defined scope.

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