chr3-20183961-T-C
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 8P and 1B. PP5_Very_StrongBS2_Supporting
The NM_001199251.3(SGO1):βc.67A>Gβ(p.Lys23Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000164 in 1,612,714 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β β ).
Frequency
Consequence
NM_001199251.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152234Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000188 AC: 47AN: 250128Hom.: 0 AF XY: 0.000192 AC XY: 26AN XY: 135160
GnomAD4 exome AF: 0.000167 AC: 244AN: 1460480Hom.: 0 Cov.: 31 AF XY: 0.000154 AC XY: 112AN XY: 726440
GnomAD4 genome AF: 0.000138 AC: 21AN: 152234Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74370
ClinVar
Submissions by phenotype
Chronic atrial and intestinal dysrhythmia Pathogenic:3
The missense c.67A>G p.Lys23Glu variant in SGO1 gene has been reported in homozygous state in multiple individuals affected with gastrointestinal disorder Chetaille et al., 2014. In vitro studies in patient fibroblasts with homozygous p.Lys23Glu suggest abnormal cell progression, cell signalling, epigenetic modifications, and protein expression compared to controls Chetaille et al., 2014. The variant is reported with allele frequency of 0.02% in gnomAD Exomes and is novel not in any individuals in 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic multiple submissions. The amino acid change p.Lys23Glu in SGO1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Lys at position 23 is changed to a Glu changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Pathogenic. -
- -
- -
not provided Pathogenic:1
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In vitro studies in patient fibroblasts with homozygous p.K23E suggest abnormal cell progression, cell signalling, epigenetic modifications, and protein expression compared to controls (Chetaille et al., 2014; Piche et al., 2019); This variant is associated with the following publications: (PMID: 31516082, 30739867, 25282101, 35799243, 32213217, 33953173) -
SGO1-related disorder Pathogenic:1
The SGO1 c.67A>G variant is predicted to result in the amino acid substitution p.Lys23Glu. This missense change has been documented in the homozygous state in multiple unrelated individuals with chronic atrial and intestinal dysrhythmia, and functional studies support its pathogenicity (Chetaille et al 2014. PubMed ID: 25282101; PichΓ© et al. 2019. PubMed ID: 30739867). This variant is reported in 0.031% of alleles in individuals of Latino descent in gnomAD. This variant is interpreted as likely pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at