chr1-12234363-G-C
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP2PP3_Strong
The NM_015378.4(VPS13D):āc.97G>Cā(p.Gly33Arg) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,460,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/20 in silico tools predict a damaging outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_015378.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VPS13D | NM_015378.4 | c.97G>C | p.Gly33Arg | missense_variant, splice_region_variant | 2/70 | ENST00000620676.6 | |
VPS13D | NM_018156.4 | c.97G>C | p.Gly33Arg | missense_variant, splice_region_variant | 2/69 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS13D | ENST00000620676.6 | c.97G>C | p.Gly33Arg | missense_variant, splice_region_variant | 2/70 | 1 | NM_015378.4 | P3 | |
VPS13D | ENST00000613099.4 | c.97G>C | p.Gly33Arg | missense_variant, splice_region_variant | 2/69 | 1 | A1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250792Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135568
GnomAD4 exome AF: 0.0000329 AC: 48AN: 1460448Hom.: 0 Cov.: 29 AF XY: 0.0000275 AC XY: 20AN XY: 726690
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 22, 2024 | The c.97G>C (p.G33R) alteration is located in exon 2 (coding exon 1) of the VPS13D gene. This alteration results from a G to C substitution at nucleotide position 97, causing the glycine (G) at amino acid position 33 to be replaced by an arginine (R). The p.G33R alteration is predicted to be deleterious by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at