17-75830431-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_199242.3(UNC13D):āc.2761C>Gā(p.Arg921Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000505 in 1,585,614 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R921C) has been classified as Uncertain significance.
Frequency
Consequence
NM_199242.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UNC13D | NM_199242.3 | c.2761C>G | p.Arg921Gly | missense_variant | 29/32 | ENST00000207549.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UNC13D | ENST00000207549.9 | c.2761C>G | p.Arg921Gly | missense_variant | 29/32 | 1 | NM_199242.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152156Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000248 AC: 5AN: 201436Hom.: 0 AF XY: 0.0000185 AC XY: 2AN XY: 108298
GnomAD4 exome AF: 0.00000488 AC: 7AN: 1433458Hom.: 0 Cov.: 34 AF XY: 0.00000422 AC XY: 3AN XY: 710468
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152156Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74310
ClinVar
Submissions by phenotype
Familial hemophagocytic lymphohistiocytosis 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 18, 2022 | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 921 of the UNC13D protein (p.Arg921Gly). This variant is present in population databases (no rsID available, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with UNC13D-related conditions. 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: "Benign"; 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at