chr17-48032160-C-T

Variant names:

• chr17-48032160-C-T
• NM_016429.4:c.490G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.793

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016429.4. 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
	COPZ2	NM_016429.4	MANE Select	c.490G>A	p.Gly164Ser	missense	Exon 6 of 9	NP_057513.1	Q9P299

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COPZ2	ENST00000621465.5	TSL:1 MANE Select	c.490G>A	p.Gly164Ser	missense	Exon 6 of 9	ENSP00000480707.1	Q9P299
	COPZ2	ENST00000861305.1		c.484G>A	p.Gly162Ser	missense	Exon 6 of 9	ENSP00000531364.1
	COPZ2	ENST00000861309.1		c.490G>A	p.Gly164Ser	missense	Exon 6 of 9	ENSP00000531368.1

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	0.13
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
M_CAP	Benign	0.0091	T
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.44	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.3
PrimateAI	Uncertain	0.67	T
Sift4G	Uncertain	0.024	D
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

Other links and lift over

hg19: chr17-46109526;