chr3-32158948-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PP3_ModerateBP6BS2
The NM_015141.4(GPD1L):c.691C>T(p.Arg231Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,613,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_015141.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152210Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000108 AC: 27AN: 250868Hom.: 0 AF XY: 0.0000884 AC XY: 12AN XY: 135750
GnomAD4 exome AF: 0.0000438 AC: 64AN: 1461786Hom.: 0 Cov.: 34 AF XY: 0.0000440 AC XY: 32AN XY: 727184
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74364
ClinVar
Submissions by phenotype
not provided Uncertain:1
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Cardiovascular phenotype Uncertain:1
The p.R231C variant (also known as c.691C>T), located in coding exon 6 of the GPD1L gene, results from a C to T substitution at nucleotide position 691. The arginine at codon 231 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
not specified Benign:1
Variant summary: GPD1L c.691C>T (p.Arg231Cys) results in a non-conservative amino acid change located in the Glycerol-3-phosphate dehydrogenase, NAD-dependent, C-terminal domain (IPR006109) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00011 in 250868 control chromosomes (gnomAD). The observed variant frequency is approximately 21 fold of the estimated maximal expected allele frequency for a pathogenic variant in GPD1L causing Brugada Syndrome phenotype (5e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.691C>T in individuals affected with Brugada Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely benign (n=1), and one laboratory classified the variant as uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as likely benign. -
Brugada syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at