NM_016057.3:c.37G>A

Variant names:

• chr12-54340565-G-A
• NM_016057.3:c.37G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016057.3(COPZ1):​c.37G>A​(p.Val13Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: COPZ1 NM_016057.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.87
• Publications: 0 publications found

Genes affected

COPZ1 (HGNC:2243): (COPI coat complex subunit zeta 1) This gene encodes a subunit of the cytoplasmic coatamer protein complex, which is involved in autophagy and intracellular protein trafficking. The coatomer protein complex is comprised of seven subunits and functions as the coat protein of coat protein complex (COP)I-vesicles. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

ENSG00000258344 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31070033).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016057.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COPZ1	NM_016057.3	MANE Select	c.37G>A	p.Val13Ile	missense	Exon 2 of 9	NP_057141.1	P61923-1
	COPZ1	NM_001271736.2		c.61G>A	p.Val21Ile	missense	Exon 2 of 9	NP_001258665.1	P61923-4
	COPZ1	NM_001271735.2		c.37G>A	p.Val13Ile	missense	Exon 2 of 8	NP_001258664.1	P61923-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COPZ1	ENST00000262061.7	TSL:1 MANE Select	c.37G>A	p.Val13Ile	missense	Exon 2 of 9	ENSP00000262061.2	P61923-1
	COPZ1	ENST00000549043.5	TSL:1	c.61G>A	p.Val21Ile	missense	Exon 2 of 9	ENSP00000449270.1	P61923-4
	COPZ1	ENST00000550027.5	TSL:1	n.62G>A		non_coding_transcript_exon	Exon 2 of 7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.065
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.56	N
PhyloP100		8.9
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.24
Sift	Benign	0.70	T
Sift4G	Benign	0.78	T
Polyphen		0.0010	B
Vest4		0.72
MutPred		0.53		Gain of catalytic residue at L10 (P = 8e-04)
MVP		0.54
MPC		0.34
ClinPred		0.92	D
GERP RS		4.8
PromoterAI		-0.019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.42
Mutation Taster		=172/128	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr12-54734349;