rs763117746
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The ENST00000207549.9(UNC13D):c.2293G>T(p.Glu765Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. E765E) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
ENST00000207549.9 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
UNC13D | NM_199242.3 | c.2293G>T | p.Glu765Ter | stop_gained | 23/32 | ENST00000207549.9 | NP_954712.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
UNC13D | ENST00000207549.9 | c.2293G>T | p.Glu765Ter | stop_gained | 23/32 | 1 | NM_199242.3 | ENSP00000207549 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000440 AC: 1AN: 227158Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 124604
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1442244Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 717672
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Familial hemophagocytic lymphohistiocytosis 3 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 20, 2018 | This variant has not been reported in the literature in individuals with UNC13D-related disease. Loss-of-function variants in UNC13D are known to be pathogenic (PMID: 14622600). For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu765*) in the UNC13D gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at