rs587780462
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_018344.6(SLC29A3):c.1228C>T(p.Gln410Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. Q410Q) has been classified as Likely benign.
Frequency
Consequence
NM_018344.6 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC29A3 | NM_018344.6 | c.1228C>T | p.Gln410Ter | stop_gained | 6/6 | ENST00000373189.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC29A3 | ENST00000373189.6 | c.1228C>T | p.Gln410Ter | stop_gained | 6/6 | 1 | NM_018344.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251400Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135888
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461870Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2AN XY: 727240
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74356
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Nov 10, 2022 | Mentioned in published literature as a variant previously reported in ClinVar in association with histiocytosis-lymphadenopathy plus syndrome (Noavar et al., 2019), but no cases with detailed clinical and segregation information have been previously reported in published literature to our knowledge; Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 85 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); This variant is associated with the following publications: (PMID: 31464584) - |
H syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 03, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at