rs373521245

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_004371.4(COPA):​c.3533G>C​(p.Arg1178Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1178H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

COPA
NM_004371.4 missense

Scores

7
6
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.03
Variant links:
Genes affected
COPA (HGNC:2230): (COPI coat complex subunit alpha) In eukaryotic cells, protein transport between the endoplasmic reticulum and Golgi compartments is mediated in part by non-clathrin-coated vesicular coat proteins (COPs). Seven coat proteins have been identified, and they represent subunits of a complex known as coatomer. The subunits are designated alpha-COP, beta-COP, beta-prime-COP, gamma-COP, delta-COP, epsilon-COP, and zeta-COP. The alpha-COP, encoded by COPA, shares high sequence similarity with RET1P, the alpha subunit of the coatomer complex in yeast. Also, the N-terminal 25 amino acids of alpha-COP encode the bioactive peptide, xenin, which stimulates exocrine pancreatic secretion and may act as a gastrointestinal hormone. Alternative splicing results in multiple splice forms encoding distinct isoforms. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.829

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COPANM_004371.4 linkc.3533G>C p.Arg1178Pro missense_variant Exon 32 of 33 ENST00000241704.8 NP_004362.2 P53621-1
COPANM_001098398.2 linkc.3560G>C p.Arg1187Pro missense_variant Exon 32 of 33 NP_001091868.1 P53621-2
LOC107985219XR_001738265.2 linkn.537-683C>G intron_variant Intron 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COPAENST00000241704.8 linkc.3533G>C p.Arg1178Pro missense_variant Exon 32 of 33 1 NM_004371.4 ENSP00000241704.7 P53621-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461890
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.020
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.27
.;.;T;.;.
Eigen
Pathogenic
0.75
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D;D;D;D;D
M_CAP
Benign
0.060
D
MetaRNN
Pathogenic
0.83
D;D;D;D;D
MetaSVM
Benign
-0.40
T
MutationAssessor
Uncertain
2.7
.;.;M;.;.
PrimateAI
Uncertain
0.68
T
PROVEAN
Pathogenic
-5.6
.;D;D;.;.
REVEL
Uncertain
0.41
Sift
Benign
0.062
.;T;D;.;.
Sift4G
Benign
0.15
.;T;T;.;.
Polyphen
1.0
.;D;D;.;.
Vest4
0.85, 0.86
MutPred
0.66
.;.;Loss of solvent accessibility (P = 0.0219);.;.;
MVP
0.71
MPC
0.75
ClinPred
0.99
D
GERP RS
5.1
Varity_R
0.84
gMVP
0.90

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-160260364; API