rs759069275
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_177550.5(SLC13A5):c.338C>T(p.Thr113Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000483 in 1,613,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. T113T) has been classified as Likely benign.
Frequency
Consequence
NM_177550.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC13A5 | NM_177550.5 | c.338C>T | p.Thr113Met | missense_variant | 3/12 | ENST00000433363.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC13A5 | ENST00000433363.7 | c.338C>T | p.Thr113Met | missense_variant | 3/12 | 1 | NM_177550.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152210Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000521 AC: 13AN: 249498Hom.: 0 AF XY: 0.0000740 AC XY: 10AN XY: 135060
GnomAD4 exome AF: 0.0000499 AC: 73AN: 1461542Hom.: 0 Cov.: 31 AF XY: 0.0000646 AC XY: 47AN XY: 727058
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74358
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 25 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 15, 2022 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 113 of the SLC13A5 protein (p.Thr113Met). This variant is present in population databases (rs759069275, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with SLC13A5-related conditions. ClinVar contains an entry for this variant (Variation ID: 451860). 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 methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 23, 2022 | The c.338C>T (p.T113M) alteration is located in exon 3 (coding exon 3) of the SLC13A5 gene. This alteration results from a C to T substitution at nucleotide position 338, causing the threonine (T) at amino acid position 113 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 15, 2018 | A variant of uncertain significance has been identified in the SLC13A5 gene. The T113M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The T113M variant is observed in 9/30668 (0.03%) alleles from individuals of South Asian background (Lek et al., 2016). In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. However, the T113M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at