rs3812883
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_020751.3(COG6):c.94T>A(p.Cys32Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 1,600,520 control chromosomes in the GnomAD database, including 140,288 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C32F) has been classified as Uncertain significance.
Frequency
Consequence
NM_020751.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COG6 | NM_020751.3 | c.94T>A | p.Cys32Ser | missense_variant | 1/19 | ENST00000455146.8 | |
COG6 | NM_001145079.2 | c.94T>A | p.Cys32Ser | missense_variant | 1/19 | ||
COG6 | XM_011535168.2 | c.94T>A | p.Cys32Ser | missense_variant | 1/20 | ||
COG6 | NR_026745.1 | n.194T>A | non_coding_transcript_exon_variant | 1/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COG6 | ENST00000455146.8 | c.94T>A | p.Cys32Ser | missense_variant | 1/19 | 1 | NM_020751.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.439 AC: 66659AN: 152014Hom.: 15004 Cov.: 33
GnomAD3 exomes AF: 0.458 AC: 104169AN: 227446Hom.: 24692 AF XY: 0.455 AC XY: 56353AN XY: 123936
GnomAD4 exome AF: 0.411 AC: 594656AN: 1448386Hom.: 125266 Cov.: 49 AF XY: 0.414 AC XY: 298060AN XY: 719562
GnomAD4 genome ? AF: 0.439 AC: 66720AN: 152134Hom.: 15022 Cov.: 33 AF XY: 0.442 AC XY: 32888AN XY: 74382
ClinVar
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 14, 2014 | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 08, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
COG6-ongenital disorder of glycosylation Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
COG6-ongenital disorder of glycosylation;C3809160:Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at