17-48032160-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016429.4(COPZ2):c.490G>A(p.Gly164Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COPZ2 NM_016429.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.27

Genes affected

COPZ2 (HGNC:19356): (COPI coat complex subunit zeta 2) This gene encodes a member of the adaptor complexes small subunit family. The encoded protein is a subunit of the coatomer protein complex, a seven-subunit complex that functions in the formation of COPI-type, non-clathrin-coated vesicles. COPI vesicles function in the retrograde Golgi-to-ER transport of dilysine-tagged proteins. [provided by RefSeq, Feb 2014]

ACMG classification

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, 0.793

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COPZ2	NM_016429.4	c.490G>A	p.Gly164Ser	missense_variant	6/9	ENST00000621465.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COPZ2	ENST00000621465.5	c.490G>A	p.Gly164Ser	missense_variant	6/9	1	NM_016429.4	P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.490G>A (p.G164S) alteration is located in exon 6 (coding exon 6) of the COPZ2 gene. This alteration results from a G to A substitution at nucleotide position 490, causing the glycine (G) at amino acid position 164 to be replaced by a serine (S). 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	0.13
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.33
Cadd	Pathogenic	27
Dann	Uncertain	0.99
DEOGEN2	Benign	0.19	T;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.0091	T
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Benign	-0.44	T
MutationAssessor	Uncertain	2.3	M;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.67	T
Sift4G	Uncertain	0.024	D;T
Polyphen		0.55	P;.
Vest4		0.63
MutPred		0.73		Gain of glycosylation at G164 (P = 0.0126);.;
MVP		0.40
ClinPred		0.94	D
GERP RS		4.6
Varity_R		0.15
gMVP		0.69

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: chr17-46109526;