9-77228167-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_033305.3(VPS13A):c.1498G>T(p.Val500Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,452,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_033305.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VPS13A | NM_033305.3 | c.1498G>T | p.Val500Phe | missense_variant | Exon 17 of 72 | ENST00000360280.8 | NP_150648.2 | |
VPS13A | NM_001018037.2 | c.1498G>T | p.Val500Phe | missense_variant | Exon 17 of 71 | NP_001018047.1 | ||
VPS13A | NM_015186.4 | c.1498G>T | p.Val500Phe | missense_variant | Exon 17 of 69 | NP_056001.1 | ||
VPS13A | NM_001018038.3 | c.1498G>T | p.Val500Phe | missense_variant | Exon 17 of 69 | NP_001018048.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VPS13A | ENST00000360280.8 | c.1498G>T | p.Val500Phe | missense_variant | Exon 17 of 72 | 1 | NM_033305.3 | ENSP00000353422.3 | ||
VPS13A | ENST00000376636.7 | c.1498G>T | p.Val500Phe | missense_variant | Exon 17 of 71 | 1 | ENSP00000365823.3 | |||
VPS13A | ENST00000643348.1 | c.1498G>T | p.Val500Phe | missense_variant | Exon 17 of 69 | ENSP00000493592.1 | ||||
VPS13A | ENST00000645632.1 | c.1498G>T | p.Val500Phe | missense_variant | Exon 17 of 69 | ENSP00000496361.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000412 AC: 1AN: 242574Hom.: 0 AF XY: 0.00000762 AC XY: 1AN XY: 131204
GnomAD4 exome AF: 0.00000207 AC: 3AN: 1452158Hom.: 0 Cov.: 30 AF XY: 0.00000416 AC XY: 3AN XY: 721904
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.1498G>T (p.V500F) alteration is located in exon 17 (coding exon 17) of the VPS13A gene. This alteration results from a G to T substitution at nucleotide position 1498, causing the valine (V) at amino acid position 500 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
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. This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 500 of the VPS13A protein (p.Val500Phe). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with VPS13A-related conditions. ClinVar contains an entry for this variant (Variation ID: 1511037). 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 VPS13A protein function. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at