NM_017890.5:c.11387C>T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_017890.5(VPS13B):c.11387C>T(p.Ser3796Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000756 in 1,614,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. S3796S) has been classified as Likely benign.
Frequency
Consequence
NM_017890.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VPS13B | ENST00000358544.7 | c.11387C>T | p.Ser3796Leu | missense_variant | Exon 59 of 62 | 1 | NM_017890.5 | ENSP00000351346.2 | ||
VPS13B | ENST00000357162.7 | c.11312C>T | p.Ser3771Leu | missense_variant | Exon 59 of 62 | 1 | NM_152564.5 | ENSP00000349685.2 |
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152062Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000636 AC: 16AN: 251432Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135890
GnomAD4 exome AF: 0.0000705 AC: 103AN: 1461886Hom.: 0 Cov.: 30 AF XY: 0.0000729 AC XY: 53AN XY: 727244
GnomAD4 genome AF: 0.000125 AC: 19AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74386
ClinVar
Submissions by phenotype
Cohen syndrome Uncertain:3
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This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 3796 of the VPS13B protein (p.Ser3796Leu). This variant is present in population databases (rs142516047, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. ClinVar contains an entry for this variant (Variation ID: 528849). 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: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). 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. -
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Inborn genetic diseases Uncertain:1
The p.S3796L variant (also known as c.11387C>T), located in coding exon 58 of the VPS13B gene, results from a C to T substitution at nucleotide position 11387. The serine at codon 3796 is replaced by leucine, an amino acid with 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 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 -
VPS13B-related disorder Uncertain:1
The VPS13B c.11312C>T variant is predicted to result in the amino acid substitution p.Ser3771Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.028% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at