22-32043315-G-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong
The NM_000343.4(SLC5A1):c.34G>A(p.Ala12Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. A12V) has been classified as Likely benign.
Frequency
Consequence
NM_000343.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC5A1 | NM_000343.4 | c.34G>A | p.Ala12Thr | missense_variant | 1/15 | ENST00000266088.9 | |
SLC5A1 | XM_011530331.2 | c.34G>A | p.Ala12Thr | missense_variant | 1/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC5A1 | ENST00000266088.9 | c.34G>A | p.Ala12Thr | missense_variant | 1/15 | 1 | NM_000343.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152218Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000478 AC: 12AN: 250806Hom.: 0 AF XY: 0.0000664 AC XY: 9AN XY: 135644
GnomAD4 exome AF: 0.0000506 AC: 74AN: 1461814Hom.: 0 Cov.: 31 AF XY: 0.0000468 AC XY: 34AN XY: 727208
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152218Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74352
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 12, 2021 | The c.34G>A (p.A12T) alteration is located in exon 1 (coding exon 1) of the SLC5A1 gene. This alteration results from a G to A substitution at nucleotide position 34, causing the alanine (A) at amino acid position 12 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Congenital glucose-galactose malabsorption Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 19, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 12 of the SLC5A1 protein (p.Ala12Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SLC5A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1005551). 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 threonine 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at