8-99821393-G-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_152564.5(VPS13B):c.9094G>T(p.Asp3032Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000613 in 1,613,786 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_152564.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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VPS13B | ENST00000358544.7 | c.9169G>T | p.Asp3057Tyr | missense_variant | Exon 50 of 62 | 1 | NM_017890.5 | ENSP00000351346.2 | ||
VPS13B | ENST00000357162.7 | c.9094G>T | p.Asp3032Tyr | missense_variant | Exon 50 of 62 | 1 | NM_152564.5 | ENSP00000349685.2 |
Frequencies
GnomAD3 genomes AF: 0.000723 AC: 110AN: 152144Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000593 AC: 149AN: 251098Hom.: 1 AF XY: 0.000619 AC XY: 84AN XY: 135678
GnomAD4 exome AF: 0.000601 AC: 879AN: 1461642Hom.: 0 Cov.: 31 AF XY: 0.000627 AC XY: 456AN XY: 727126
GnomAD4 genome AF: 0.000723 AC: 110AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.000767 AC XY: 57AN XY: 74322
ClinVar
Submissions by phenotype
Cohen syndrome Uncertain:3Benign:2
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This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
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VPS13B NM_017890.4 exon 50 p.Asp3057Tyr (c.9169G>T): This variant has not been reported in the literature but is present in 0.2% (46/25108) of Finnish alleles and in 1 homozygote in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/8-100833621-G-T?dataset=gnomad_r2_1). This variant is present in ClinVar, with classifications ranging from benign to Uncertain significance (Variation ID:95873). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -
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not provided Uncertain:2Benign:2
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VPS13B: BP4 -
not specified Uncertain:1
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Inborn genetic diseases Uncertain:1
The c.9169G>T (p.D3057Y) alteration is located in exon 50 (coding exon 49) of the VPS13B gene. This alteration results from a G to T substitution at nucleotide position 9169, causing the aspartic acid (D) at amino acid position 3057 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
VPS13B-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at