X-140503952-A-G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_005634.3(SOX3):āc.1109T>Cā(p.Met370Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000174 in 1,150,493 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_005634.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000277 AC: 3AN: 108430Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 31822
GnomAD3 exomes AF: 0.0000184 AC: 2AN: 108937Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 30839
GnomAD4 exome AF: 0.0000163 AC: 17AN: 1042063Hom.: 0 Cov.: 31 AF XY: 0.00000605 AC XY: 2AN XY: 330347
GnomAD4 genome AF: 0.0000277 AC: 3AN: 108430Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 31822
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 370 of the SOX3 protein (p.Met370Thr). 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. 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with SOX3-related conditions. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at