rs777619516
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_199242.3(UNC13D):c.71G>A(p.Arg24His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,460,290 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R24C) has been classified as Uncertain significance.
Frequency
Consequence
NM_199242.3 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UNC13D | NM_199242.3 | c.71G>A | p.Arg24His | missense_variant | 1/32 | ENST00000207549.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UNC13D | ENST00000207549.9 | c.71G>A | p.Arg24His | missense_variant | 1/32 | 1 | NM_199242.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000562 AC: 14AN: 249264Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135168
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1460290Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 726506
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Familial hemophagocytic lymphohistiocytosis 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 26, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 24 of the UNC13D protein (p.Arg24His). This variant is present in population databases (rs777619516, gnomAD 0.03%). This missense change has been observed in individual(s) with hemophagocytic lymphohistiocytosis (PMID: 29665027). ClinVar contains an entry for this variant (Variation ID: 568424). 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: "Possibly Damaging"; 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