chr13-39655806-C-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_020751.3(COG6):c.80C>G(p.Thr27Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000281 in 1,599,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. T27I) has been classified as Uncertain significance.
Frequency
Consequence
NM_020751.3 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 | UniProt |
---|---|---|---|---|---|---|---|
COG6 | NM_020751.3 | c.80C>G | p.Thr27Ser | missense_variant | 1/19 | ENST00000455146.8 | |
COG6 | NM_001145079.2 | c.80C>G | p.Thr27Ser | missense_variant | 1/19 | ||
COG6 | XM_011535168.2 | c.80C>G | p.Thr27Ser | missense_variant | 1/20 | ||
COG6 | NR_026745.1 | n.180C>G | non_coding_transcript_exon_variant | 1/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COG6 | ENST00000455146.8 | c.80C>G | p.Thr27Ser | missense_variant | 1/19 | 1 | NM_020751.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152236Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000987 AC: 22AN: 222960Hom.: 0 AF XY: 0.0000576 AC XY: 7AN XY: 121474
GnomAD4 exome AF: 0.0000228 AC: 33AN: 1446924Hom.: 0 Cov.: 41 AF XY: 0.0000167 AC XY: 12AN XY: 718608
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152236Hom.: 0 Cov.: 34 AF XY: 0.000134 AC XY: 10AN XY: 74380
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 03, 2022 | The c.80C>G (p.T27S) alteration is located in exon 1 (coding exon 1) of the COG6 gene. This alteration results from a C to G substitution at nucleotide position 80, causing the threonine (T) at amino acid position 27 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
COG6-ongenital disorder of glycosylation;C3809160:Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 30, 2021 | This sequence change replaces threonine with serine at codon 27 of the COG6 protein (p.Thr27Ser). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and serine. This variant is present in population databases (rs776763438, ExAC 0.04%). This variant has not been reported in the literature in individuals affected with COG6-related conditions. 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 tolerated. 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