NM_001032221.6:c.166G>C

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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

Variant NM_001032221.6:c.166G>C could not be validated: VariantValidator reports the reference nucleotide at NM_001032221.6 position 166 is A, not G. No gene, protein consequence, population frequency, ClinVar classification, or literature evidence could be obtained.

No ACMG/AMP criteria could be met due to complete absence of evidence across all data sources. Classification is not possible with available data.

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	Variant is a substitution (c.166G>C) not falling into any null-variant bucket (nonsense, frameshift, canonical splice, initiation codon, or exon deletion). PVS1 is reserved for null variants in genes where loss-of-function is an established disease mechanism; gene-level LOF eligibility also could not be established.	pvs1_generic_framework
PS1	Not assessed	No protein-level consequence could be determined, precluding identification of a same-amino-acid-change comparator with a prior pathogenic classification.
PS2	Not assessed	No de novo data available; variant could not be identified in ClinVar or literature sources.
PS3	Not assessed	No functional studies identified; variant not found in any literature or database source.
PS4	Not assessed	No case-control or prevalence data available; variant absent from ClinVar and gnomAD queries could not be completed due to failed normalization.
PS5	Not assessed	No reputable source (ClinVar expert panel, clinical laboratory, curated database) has reported this variant as pathogenic.
PM1	Not assessed	Cannot assess whether the variant resides in a mutational hot spot or critical functional domain because the gene and protein domain architecture remain unknown.
PM2	Not assessed	Population frequency could not be determined; gnomAD v2.1 and v4.1 queries returned null, and gnomAD-Canada returned zero alleles observed (AC=0) with zero total alleles (AN=0), indicating no population coverage rather than true absence.
PM5	Not assessed	No same-residue comparator variants could be identified; protein-level consequence is unknown and PM5 candidate harvesting was not feasible.
PM6	Not assessed	No de novo observations available; variant absent from ClinVar and literature.
PP1	Not assessed	No co-segregation data available; no family studies identified.
PP2	Not assessed	Cannot assess missense constraint; HCI Prior scores are unavailable (gene unknown, no coordinates) and the gene's benign missense rate cannot be evaluated.
PP3	Not assessed	No in silico prediction scores available; REVEL and BayesDel queries were skipped (no SNV coordinates), SpliceAI delta scores are null, and no other computational evidence could be evaluated.
PP4	Not assessed	No patient phenotype or family history data available for this case.
PP5	Not assessed	No reputable source has reported this variant; ClinVar classification is absent and no publications mention it.
BA1	Not assessed	Population allele frequency could not be determined; gnomAD queries returned null due to failed variant normalization.
BS1	Not assessed	Population allele frequency could not be determined; gnomAD queries returned null due to failed variant normalization.
BS2	Not assessed	No homozygous or hemizygous observations in controls could be assessed; variant absent from all databases.
BS3	Not assessed	No functional studies identified that demonstrate a benign effect; variant not found in any literature or database source.
BS4	Not assessed	No non-segregation data available; no family studies identified.
BP1	Not assessed	Cannot assess whether a missense variant in this gene should be designated BP1 (observed with a known pathogenic truncating variant) because the gene is unknown.
BP2	Not assessed	No data on observation in trans with a pathogenic variant; variant not found in any database or literature source.
BP3	N/A	BP3 applies to in-frame deletions or insertions in repetitive regions without a known function; this variant is a substitution.
BP4	Not assessed	No in silico prediction scores available to support a benign interpretation; REVEL, BayesDel, and SpliceAI are all unavailable due to missing genomic coordinates.
BP5	Not assessed	No alternate molecular basis for disease has been identified in this case; variant not found in any database.
BP6	Not assessed	No reputable source has reported this variant; ClinVar classification is absent.
BP7	Not assessed	Cannot determine whether this is a synonymous variant with no predicted splice effect because the variant class and SpliceAI scores are unavailable.

Disclaimer: The content and results provided by LYFE Sciences are for research and educational purposes only and must not be used as a substitute for professional medical judgment, diagnosis, or treatment. Always consult a qualified healthcare professional before making any clinical decisions.