chr7-107767596-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000111.3(SLC26A3):c.2254C>T(p.Arg752Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000348 in 1,607,886 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R752H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000111.3 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 |
---|---|---|---|---|---|---|---|
SLC26A3 | NM_000111.3 | c.2254C>T | p.Arg752Cys | missense_variant | 20/21 | ENST00000340010.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC26A3 | ENST00000340010.10 | c.2254C>T | p.Arg752Cys | missense_variant | 20/21 | 1 | NM_000111.3 | P1 | |
SLC26A3 | ENST00000379083.7 | c.*1811C>T | 3_prime_UTR_variant, NMD_transcript_variant | 19/20 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152014Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000758 AC: 19AN: 250814Hom.: 0 AF XY: 0.0000590 AC XY: 8AN XY: 135582
GnomAD4 exome AF: 0.0000343 AC: 50AN: 1455754Hom.: 0 Cov.: 29 AF XY: 0.0000386 AC XY: 28AN XY: 724582
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152132Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74360
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 05, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 752 of the SLC26A3 protein (p.Arg752Cys). This variant is present in population databases (rs776888978, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with SLC26A3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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