chr8-99111227-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_017890.5(VPS13B):c.710G>A(p.Arg237His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,601,318 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. R237C) has been classified as Uncertain significance.
Frequency
Consequence
NM_017890.5 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 |
---|---|---|---|---|---|---|---|
VPS13B | NM_017890.5 | c.710G>A | p.Arg237His | missense_variant | 6/62 | ENST00000358544.7 | |
VPS13B | NM_152564.5 | c.710G>A | p.Arg237His | missense_variant | 6/62 | ENST00000357162.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS13B | ENST00000358544.7 | c.710G>A | p.Arg237His | missense_variant | 6/62 | 1 | NM_017890.5 | ||
VPS13B | ENST00000357162.7 | c.710G>A | p.Arg237His | missense_variant | 6/62 | 1 | NM_152564.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000659 AC: 1AN: 151684Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000288 AC: 7AN: 243424Hom.: 0 AF XY: 0.0000228 AC XY: 3AN XY: 131458
GnomAD4 exome AF: 0.0000117 AC: 17AN: 1449634Hom.: 0 Cov.: 31 AF XY: 0.0000125 AC XY: 9AN XY: 720560
GnomAD4 genome AF: 0.00000659 AC: 1AN: 151684Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74056
ClinVar
Submissions by phenotype
Cohen syndrome Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 25, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 237 of the VPS13B protein (p.Arg237His). This variant is present in population databases (rs751804274, gnomAD 0.01%). This missense change has been observed in individual(s) with developmental disorder (PMID: 32959227). ClinVar contains an entry for this variant (Variation ID: 578539). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt VPS13B protein function. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at