chr8-54458381-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_022454.4(SOX17):c.243C>G(p.Asp81Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,612,770 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D81N) has been classified as Uncertain significance.
Frequency
Consequence
NM_022454.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOX17 | NM_022454.4 | c.243C>G | p.Asp81Glu | missense_variant | 1/2 | ENST00000297316.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOX17 | ENST00000297316.5 | c.243C>G | p.Asp81Glu | missense_variant | 1/2 | 1 | NM_022454.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000816 AC: 2AN: 245020Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 133588
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460558Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726602
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74358
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 24, 2021 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with SOX17-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 81 of the SOX17 protein (p.Asp81Glu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at