chr19-6772994-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_005428.4(VAV1):c.187C>T(p.Arg63Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,950 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R63H) has been classified as Uncertain significance.
Frequency
Consequence
NM_005428.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VAV1 | NM_005428.4 | c.187C>T | p.Arg63Cys | missense_variant | 1/27 | ENST00000602142.6 | |
VAV1 | NM_001258206.2 | c.187C>T | p.Arg63Cys | missense_variant | 1/26 | ||
VAV1 | NM_001258207.2 | c.187C>T | p.Arg63Cys | missense_variant | 1/26 | ||
VAV1 | XM_005259642.2 | c.187C>T | p.Arg63Cys | missense_variant | 1/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VAV1 | ENST00000602142.6 | c.187C>T | p.Arg63Cys | missense_variant | 1/27 | 1 | NM_005428.4 | P1 | |
VAV1 | ENST00000304076.6 | c.187C>T | p.Arg63Cys | missense_variant | 1/26 | 1 | |||
VAV1 | ENST00000596764.5 | c.187C>T | p.Arg63Cys | missense_variant | 1/26 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152118Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251232Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135800
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461832Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727230
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152118Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74312
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 27, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with VAV1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces arginine, a(n) basic and polar amino acid, with cysteine, a(n) neutral and slightly polar amino acid, at codon 63 of the VAV1 protein (p.Arg63Cys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at