chr17-73208326-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_018714.3(COG1):c.2818G>A(p.Ala940Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,644 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).
Frequency
Consequence
NM_018714.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COG1 | NM_018714.3 | c.2818G>A | p.Ala940Thr | missense_variant | 14/14 | ENST00000299886.9 | NP_061184.1 | |
FAM104A | NM_001098832.2 | c.*1203C>T | 3_prime_UTR_variant | 4/4 | ENST00000405159.8 | NP_001092302.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COG1 | ENST00000299886.9 | c.2818G>A | p.Ala940Thr | missense_variant | 14/14 | 1 | NM_018714.3 | ENSP00000299886 | P1 | |
FAM104A | ENST00000405159.8 | c.*1203C>T | 3_prime_UTR_variant | 4/4 | 1 | NM_001098832.2 | ENSP00000384832 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152202Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251426Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135896
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461442Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727028
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152202Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74360
ClinVar
Submissions by phenotype
COG1 congenital disorder of glycosylation Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 28, 2021 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 940 of the COG1 protein (p.Ala940Thr). This variant is present in population databases (rs144896007, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with COG1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at