chr1-12244322-C-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PM2PP2BP4_StrongBS1_Supporting
The NM_015378.4(VPS13D):āc.252C>Gā(p.Ser84Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,614,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S84T) has been classified as Uncertain significance.
Frequency
Consequence
NM_015378.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VPS13D | NM_015378.4 | c.252C>G | p.Ser84Arg | missense_variant | 4/70 | ENST00000620676.6 | |
VPS13D | NM_018156.4 | c.252C>G | p.Ser84Arg | missense_variant | 4/69 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS13D | ENST00000620676.6 | c.252C>G | p.Ser84Arg | missense_variant | 4/70 | 1 | NM_015378.4 | P3 | |
VPS13D | ENST00000613099.4 | c.252C>G | p.Ser84Arg | missense_variant | 4/69 | 1 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152150Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000955 AC: 24AN: 251352Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135866
GnomAD4 exome AF: 0.0000192 AC: 28AN: 1461864Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727230
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152150Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74318
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 22, 2022 | This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 84 of the VPS13D protein (p.Ser84Arg). This variant is present in population databases (rs747997002, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with VPS13D-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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