1-160290555-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_004371.4(COPA):c.3552G>T(p.Lys1184Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: COPA NM_004371.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.65

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]

LOC107985219 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, COPA
• BP4: Computational evidence support a benign effect (MetaRNN=0.4220158).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COPA	NM_004371.4	c.3552G>T	p.Lys1184Asn	missense_variant	32/33	ENST00000241704.8
LOC107985219	XR_001738265.2	n.537-702C>A		intron_variant, non_coding_transcript_variant
COPA	NM_001098398.2	c.3579G>T	p.Lys1193Asn	missense_variant	32/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COPA	ENST00000241704.8	c.3552G>T	p.Lys1184Asn	missense_variant	32/33	1	NM_004371.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727246

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autoimmune interstitial lung disease-arthritis syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Sep 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
Cadd	Benign	23
Dann	Uncertain	1.0
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D;D;D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.42	T;T;T;T;T
MetaSVM	Benign	-0.74	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.65	T
Polyphen		0.99, 0.95	.;D;P;.;.
Vest4		0.74, 0.75
MutPred		0.54		.;.;Loss of methylation at K1184 (P = 0.0022);.;.;
MVP		0.67
MPC		1.1
ClinPred		0.97	D
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.41
gMVP		0.91

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

Other links and lift over

dbSNP: rs1265302722; hg19: chr1-160260345;