1-160290511-T-C
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BS1_SupportingBS2
The NM_004371.4(COPA):āc.3596A>Gā(p.Gln1199Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_004371.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COPA | NM_004371.4 | c.3596A>G | p.Gln1199Arg | missense_variant | Exon 32 of 33 | ENST00000241704.8 | NP_004362.2 | |
COPA | NM_001098398.2 | c.3623A>G | p.Gln1208Arg | missense_variant | Exon 32 of 33 | NP_001091868.1 | ||
LOC107985219 | XR_001738265.2 | n.537-746T>C | intron_variant | Intron 2 of 2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 152200Hom.: 0 Cov.: 32 FAILED QC
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251222Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135732
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461880Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727246
GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74358
ClinVar
Submissions by phenotype
Autoimmune interstitial lung disease-arthritis syndrome Uncertain:1
This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 1199 of the COPA protein (p.Gln1199Arg). This variant is present in population databases (rs757939740, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with COPA-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COPA protein function with a negative predictive value of 80%. 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