chr10-74111990-C-G
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2
The NM_014000.3(VCL):āc.2827C>Gā(p.Pro943Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000181 in 1,614,076 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P943T) has been classified as Uncertain significance.
Frequency
Consequence
NM_014000.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VCL | NM_014000.3 | c.2827C>G | p.Pro943Ala | missense_variant | 19/22 | ENST00000211998.10 | |
VCL | NM_003373.4 | c.2746-2194C>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VCL | ENST00000211998.10 | c.2827C>G | p.Pro943Ala | missense_variant | 19/22 | 1 | NM_014000.3 | ||
VCL | ENST00000372755.7 | c.2746-2194C>G | intron_variant | 1 | P1 | ||||
VCL | ENST00000623461.3 | n.5549-2194C>G | intron_variant, non_coding_transcript_variant | 1 | |||||
VCL | ENST00000624354.3 | c.*2582C>G | 3_prime_UTR_variant, NMD_transcript_variant | 18/21 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000191 AC: 48AN: 251460Hom.: 0 AF XY: 0.000206 AC XY: 28AN XY: 135904
GnomAD4 exome AF: 0.000188 AC: 275AN: 1461892Hom.: 1 Cov.: 35 AF XY: 0.000199 AC XY: 145AN XY: 727246
GnomAD4 genome AF: 0.000112 AC: 17AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74340
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 11, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 21, 2021 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Reported in ClinVar but additional evidence is not available (ClinVar Variant ID# 192181; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 23861362, 15769782, 25351510, 16236538) - |
Primary familial dilated cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute | - | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Mar 23, 2022 | - - |
Dilated cardiomyopathy 1W Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 08, 2017 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at