rs587780461
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001126121.2(SLC25A19):c.332G>A(p.Ser111Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. S111S) has been classified as Likely benign.
Frequency
Consequence
NM_001126121.2 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 |
---|---|---|---|---|---|---|---|
SLC25A19 | NM_001126121.2 | c.332G>A | p.Ser111Asn | missense_variant | 5/8 | ENST00000416858.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC25A19 | ENST00000416858.7 | c.332G>A | p.Ser111Asn | missense_variant | 5/8 | 1 | NM_001126121.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152168Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000958 AC: 24AN: 250460Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135428
GnomAD4 exome AF: 0.0000239 AC: 35AN: 1461432Hom.: 0 Cov.: 40 AF XY: 0.0000248 AC XY: 18AN XY: 726968
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152168Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74324
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 13, 2020 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 28, 2014 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 23, 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 asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 130329). This variant has not been reported in the literature in individuals affected with SLC25A19-related conditions. This variant is present in population databases (rs587780461, gnomAD 0.07%). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 111 of the SLC25A19 protein (p.Ser111Asn). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at