rs777002036
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000366541.8(SDCCAG8):c.916G>A(p.Glu306Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000322 in 1,614,012 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. E306D) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000366541.8 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SDCCAG8 | NM_006642.5 | c.916G>A | p.Glu306Lys | missense_variant | 8/18 | ENST00000366541.8 | NP_006633.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SDCCAG8 | ENST00000366541.8 | c.916G>A | p.Glu306Lys | missense_variant | 8/18 | 1 | NM_006642.5 | ENSP00000355499 | P1 | |
SDCCAG8 | ENST00000435549.1 | c.256G>A | p.Glu86Lys | missense_variant | 3/11 | 1 | ENSP00000410200 | |||
SDCCAG8 | ENST00000463012.1 | n.276G>A | non_coding_transcript_exon_variant | 2/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000107 AC: 27AN: 251384Hom.: 0 AF XY: 0.000147 AC XY: 20AN XY: 135872
GnomAD4 exome AF: 0.0000349 AC: 51AN: 1461798Hom.: 0 Cov.: 33 AF XY: 0.0000454 AC XY: 33AN XY: 727192
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74354
ClinVar
Submissions by phenotype
SDCCAG8-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 03, 2024 | The SDCCAG8 c.916G>A variant is predicted to result in the amino acid substitution p.Glu306Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.062% of alleles in individuals of South Asian descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Senior-Loken syndrome 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Senior-Loken syndrome 7;C3889474:Bardet-Biedl syndrome 16 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 24, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 306 of the SDCCAG8 protein (p.Glu306Lys). This variant is present in population databases (rs777002036, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with SDCCAG8-related conditions. ClinVar contains an entry for this variant (Variation ID: 474960). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SDCCAG8 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. - |
Bardet-Biedl syndrome 16 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at