NM_000100.4:c.121G>A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 4P and 9B. PM1PM2BP4_StrongBP6BS1
The NM_000100.4(CSTB):c.121G>A(p.Val41Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,614,132 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000100.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000979 AC: 149AN: 152212Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00119 AC: 300AN: 251478Hom.: 2 AF XY: 0.00128 AC XY: 174AN XY: 135914
GnomAD4 exome AF: 0.00175 AC: 2556AN: 1461802Hom.: 1 Cov.: 30 AF XY: 0.00176 AC XY: 1278AN XY: 727208
GnomAD4 genome AF: 0.000985 AC: 150AN: 152330Hom.: 0 Cov.: 33 AF XY: 0.000953 AC XY: 71AN XY: 74490
ClinVar
Submissions by phenotype
Unverricht-Lundborg syndrome Uncertain:1Benign:2
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
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not provided Uncertain:1Benign:1
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not specified Benign:2
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Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
CSTB-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Progressive myoclonic epilepsy Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at