rs59841046
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_194255.4(SLC19A1):c.1367G>A(p.Arg456Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000289 in 1,593,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R456W) has been classified as Uncertain significance.
Frequency
Consequence
NM_194255.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC19A1 | NM_194255.4 | c.1367G>A | p.Arg456Gln | missense_variant | 6/6 | ENST00000311124.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC19A1 | ENST00000311124.9 | c.1367G>A | p.Arg456Gln | missense_variant | 6/6 | 1 | NM_194255.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152186Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000803 AC: 17AN: 211626Hom.: 0 AF XY: 0.0000696 AC XY: 8AN XY: 114914
GnomAD4 exome AF: 0.0000291 AC: 42AN: 1441094Hom.: 0 Cov.: 36 AF XY: 0.0000224 AC XY: 16AN XY: 714880
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152304Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74468
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 20, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with SLC19A1-related conditions. This variant is present in population databases (rs59841046, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 456 of the SLC19A1 protein (p.Arg456Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at