chr16-70481072-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_015386.3(COG4):c.2308C>T(p.Arg770Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R770R) has been classified as Likely benign.
Frequency
Consequence
NM_015386.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COG4 | NM_015386.3 | c.2308C>T | p.Arg770Cys | missense_variant | 19/19 | ENST00000323786.10 | |
COG4 | NM_001195139.2 | c.2233C>T | p.Arg745Cys | missense_variant | 18/18 | ||
COG4 | NM_001365426.1 | c.1882C>T | p.Arg628Cys | missense_variant | 20/20 | ||
COG4 | NR_158212.1 | n.2267C>T | non_coding_transcript_exon_variant | 19/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COG4 | ENST00000323786.10 | c.2308C>T | p.Arg770Cys | missense_variant | 19/19 | 1 | NM_015386.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250576Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135608
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461070Hom.: 0 Cov.: 33 AF XY: 0.0000138 AC XY: 10AN XY: 726856
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74350
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 14, 2021 | The c.2308C>T (p.R770C) alteration is located in exon 19 (coding exon 19) of the COG4 gene. This alteration results from a C to T substitution at nucleotide position 2308, causing the arginine (R) at amino acid position 770 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at