12-54340565-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COPZ1	NM_016057.3	c.37G>A	p.Val13Ile	missense_variant	Exon 2 of 9	ENST00000262061.7	NP_057141.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COPZ1	ENST00000262061.7	c.37G>A	p.Val13Ile	missense_variant	Exon 2 of 9	1	NM_016057.3	ENSP00000262061.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.37G>A (p.V13I) alteration is located in exon 2 (coding exon 2) of the COPZ1 gene. This alteration results from a G to A substitution at nucleotide position 37, causing the valine (V) at amino acid position 13 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;.;T;.;T;.;T
Eigen	Benign	-0.065
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D;D;D
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.31	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.56	.;N;.;.;N;.;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.0	N;N;N;N;N;N;N;N
REVEL	Benign	0.24
Sift	Benign	0.70	T;T;T;T;T;T;T;T
Sift4G	Benign	0.78	T;T;T;T;T;T;T;T
Polyphen		0.0010	.;B;.;.;.;.;.;.
Vest4		0.72, 0.57, 0.64, 0.67, 0.59, 0.72
MutPred		0.53		Gain of catalytic residue at L10 (P = 8e-04);Gain of catalytic residue at L10 (P = 8e-04);.;Gain of catalytic residue at L10 (P = 8e-04);Gain of catalytic residue at L10 (P = 8e-04);Gain of catalytic residue at L10 (P = 8e-04);Gain of catalytic residue at L10 (P = 8e-04);.;
MVP		0.54
MPC		0.34
ClinPred		0.92	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.42

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-54734349;