rs267607057
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4
The NM_018344.6(SLC29A3):āc.347T>Gā(p.Met116Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000116 in 1,614,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M116V) has been classified as Uncertain significance.
Frequency
Consequence
NM_018344.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC29A3 | NM_018344.6 | c.347T>G | p.Met116Arg | missense_variant | 3/6 | ENST00000373189.6 | |
LOC105378353 | XR_946051.3 | n.167-2874A>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC29A3 | ENST00000373189.6 | c.347T>G | p.Met116Arg | missense_variant | 3/6 | 1 | NM_018344.6 | P1 | |
ENST00000686111.2 | n.228-2874A>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000788 AC: 12AN: 152234Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251450Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135902
GnomAD4 exome AF: 0.000120 AC: 175AN: 1461820Hom.: 0 Cov.: 32 AF XY: 0.000113 AC XY: 82AN XY: 727214
GnomAD4 genome AF: 0.0000788 AC: 12AN: 152234Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74382
ClinVar
Submissions by phenotype
H syndrome Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 19, 2022 | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Experimental studies have shown that this missense change affects SLC29A3 function (PMID: 20595384). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SLC29A3 protein function. ClinVar contains an entry for this variant (Variation ID: 568). This missense change has been observed in individual(s) with histiocytosis-lymphadenopathy plus syndrome and/or SLC29A3-related conditions (PMID: 19336477, 29041934; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs267607057, gnomAD 0.006%). This sequence change replaces methionine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 116 of the SLC29A3 protein (p.Met116Arg). - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 03, 2010 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at