chr13-39655796-G-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_020751.3(COG6):c.70G>T(p.Ala24Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 1,598,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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.70G>T | p.Ala24Ser | missense_variant | 1/19 | ENST00000455146.8 | |
COG6 | NM_001145079.2 | c.70G>T | p.Ala24Ser | missense_variant | 1/19 | ||
COG6 | XM_011535168.2 | c.70G>T | p.Ala24Ser | missense_variant | 1/20 | ||
COG6 | NR_026745.1 | n.170G>T | non_coding_transcript_exon_variant | 1/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COG6 | ENST00000455146.8 | c.70G>T | p.Ala24Ser | missense_variant | 1/19 | 1 | NM_020751.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152244Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000900 AC: 2AN: 222264Hom.: 0 AF XY: 0.00000827 AC XY: 1AN XY: 120896
GnomAD4 exome AF: 0.00000207 AC: 3AN: 1446198Hom.: 0 Cov.: 42 AF XY: 0.00000139 AC XY: 1AN XY: 718070
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152244Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74382
ClinVar
Submissions by phenotype
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 | Apr 10, 2021 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with COG6-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with serine at codon 24 of the COG6 protein (p.Ala24Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at