NM_004371.4:c.3610A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004371.4(COPA):​c.3610A>G​(p.Thr1204Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

COPA
NM_004371.4 missense

Scores

2
7
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.34
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COPANM_004371.4 linkc.3610A>G p.Thr1204Ala missense_variant Exon 32 of 33 ENST00000241704.8 NP_004362.2 P53621-1
COPANM_001098398.2 linkc.3637A>G p.Thr1213Ala missense_variant Exon 32 of 33 NP_001091868.1 P53621-2
LOC107985219XR_001738265.2 linkn.537-760T>C intron_variant Intron 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COPAENST00000241704.8 linkc.3610A>G p.Thr1204Ala missense_variant Exon 32 of 33 1 NM_004371.4 ENSP00000241704.7 P53621-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.56
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.030
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.10
.;.;T;.;.
Eigen
Benign
0.10
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.95
D;D;D;D;D
M_CAP
Benign
0.015
T
MetaRNN
Uncertain
0.54
D;D;D;D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
.;.;L;.;.
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-0.21
.;N;N;.;.
REVEL
Benign
0.21
Sift
Benign
0.034
.;D;D;.;.
Sift4G
Benign
0.17
.;T;T;.;.
Polyphen
0.033, 0.073
.;B;B;.;.
Vest4
0.92, 0.88
MutPred
0.65
.;.;Gain of phosphorylation at T1205 (P = 0.3847);.;.;
MVP
0.88
MPC
0.54
ClinPred
0.67
D
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.27
gMVP
0.83

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1324502575; hg19: chr1-160260287; API