NM_004371.4:c.3532C>T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PP3_ModerateBS1_SupportingBS2
The NM_004371.4(COPA):c.3532C>T(p.Arg1178Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000173 in 1,614,072 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1178H) has been classified as Likely benign.
Frequency
Consequence
NM_004371.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COPA | NM_004371.4 | c.3532C>T | p.Arg1178Cys | missense_variant | Exon 32 of 33 | ENST00000241704.8 | NP_004362.2 | |
COPA | NM_001098398.2 | c.3559C>T | p.Arg1187Cys | missense_variant | Exon 32 of 33 | NP_001091868.1 | ||
LOC107985219 | XR_001738265.2 | n.537-682G>A | intron_variant | Intron 2 of 2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152188Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251452Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135892
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461884Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12AN XY: 727246
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74346
ClinVar
Submissions by phenotype
Autoimmune interstitial lung disease-arthritis syndrome Uncertain:1
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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with COPA-related conditions. This variant is present in population databases (rs745912040, gnomAD 0.009%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1178 of the COPA protein (p.Arg1178Cys). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at