NM_000264.5:c.3647A>G

· ·

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

VUS: the submitted change does not match the reference sequence (c.3647 is G, not A), so no ACMG/AMP 2015 criterion could be applied and no evidence threshold was reached.

Final determination: Under the generic ACMG/AMP 2015 fallback, no applied criteria do not meet any Pathogenic, Likely Pathogenic, Benign, or Likely Benign combination threshold; therefore the classification is 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	Not assessed: the reference base at c.3647 is G, not the submitted A, so the gene, consequence, and NMD prediction remain unresolved.	pvs1_gene_context pvs1_variant_assessment pvs1_generic_framework
PS1	Not assessed	Not assessed: no previously established pathogenic variant at the same residue could be identified, since the variant's position is unconfirmed (reference base at c.3647 is G, not A).	generic_acmg_combination_rules
PS2	Not assessed	Not assessed: no proband de novo observation or documented parental-testing result was available.	generic_acmg_combination_rules
PS3	Not assessed	Not assessed: no validated functional assay evidence was available for this variant.	generic_acmg_combination_rules
PS4	Not assessed	Not assessed: no case-control enrichment data were available because the variant's gene and genomic position could not be resolved.
PM1	Not assessed	Not assessed: the variant's residue is unconfirmed (reference base at c.3647 is G, not A), so hotspot or domain membership could not be evaluated.	generic_acmg_combination_rules
PM2	Not assessed	Not assessed: no population database evidence established that the variant is absent or rare in the general population.	generic_acmg_combination_rules
PM3	Not assessed	Not assessed: no proband, phase, or trans/cis observations were available to support a recessive mechanism.
PM4	Not assessed	Not assessed: no protein consequence or length change could be established while the c.3647 reference mismatch (G, not A) is unresolved.
PM5	Not assessed	Not assessed: no different missense change at the same residue established as pathogenic was available, and the residue itself is unconfirmed.	generic_acmg_combination_rules pm5_candidates
PM6	Not assessed	Not assessed: no case report of an apparently de novo variant without confirmed parental testing was available.	generic_acmg_combination_rules
PP1	Not assessed	Not assessed: no family segregation observations (affected relatives or informative meioses) were available.	generic_acmg_combination_rules
PP2	Not assessed	Not assessed: the gene is unresolved (reference base at c.3647 is G, not A), so its benign missense rate could not be evaluated.	generic_acmg_combination_rules
PP3	Not assessed	Not assessed: no consequence or computational prediction could be evaluated because the submitted change does not match the reference (c.3647 is G, not A).
PP4	Not assessed	Not assessed: no gene or patient phenotype context was available, so phenotype specificity could not be judged.
PP5	Not assessed	Not assessed: no ClinVar expert-panel Pathogenic or Likely pathogenic record for this exact variant was available.
BA1	Not assessed	Not assessed: the variant could not be confirmed (c.3647 reference is G, not A), and no population-frequency data were available.	generic_acmg_combination_rules
BS1	Not assessed	Not assessed: no population-frequency, prevalence, or penetrance data were available, and the variant's identity was unconfirmed.	generic_acmg_combination_rules
BS2	Not assessed	Not assessed: no unaffected homozygote or hemizygote observations with phenotype and inheritance data were available.	generic_acmg_combination_rules
BS3	Not assessed	Not assessed: no functional assay evidence demonstrating a well-established benign effect was available.	generic_acmg_combination_rules
BS4	Not assessed	Not assessed: no unaffected informative relatives with genotype and phenotype data were available.	generic_acmg_combination_rules
BP1	Not assessed	Not assessed: the gene and even the missense class are unconfirmed, and a truncating-only disease mechanism was not established.	generic_acmg_combination_rules pvs1_gene_context
BP2	Not assessed	Not assessed: no cis/trans observation with another pathogenic variant or family segregation data was available.
BP3	Not assessed	Not assessed: no evidence of an in-frame protein length change or a functionally silent repetitive-region location was available.
BP4	Not assessed	Not assessed: no validated consequence or calibrated benign computational prediction was available for this unconfirmed variant.
BP5	Not assessed	Not assessed: no affected individual, phenotype, or independent molecular diagnosis was available for this variant.
BP6	Not assessed	Not assessed: no ClinVar expert-panel Benign or Likely benign record for this exact variant was available.
BP7	Not assessed	Not assessed: synonymous status could not be established because the submitted change mismatches the reference at c.3647 (G, not A).

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