7-100091134-A-C

Position:

• chr7-100091134-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006833.5(COPS6):​c.631A>C​(p.Ser211Arg) variant causes a missense change. 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 (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COPS6 NM_006833.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.91

Genes affected

COPS6 (HGNC:21749): (COP9 signalosome subunit 6) The protein encoded by this gene is one of the eight subunits of COP9 signalosome, a highly conserved protein complex that functions as an important regulator in multiple signaling pathways. The structure and function of COP9 signalosome is similar to that of the 19S regulatory particle of 26S proteasome. COP9 signalosome has been shown to interact with SCF-type E3 ubiquitin ligases and act as a positive regulator of E3 ubiquitin ligases. This protein belongs to translation initiation factor 3 (eIF3) superfamily. It is involved in the regulation of cell cycle and likely to be a cellular cofactor for HIV-1 accessory gene product Vpr. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19480917).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COPS6	NM_006833.5	c.631A>C	p.Ser211Arg	missense_variant	7/10	ENST00000303904.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COPS6	ENST00000303904.8	c.631A>C	p.Ser211Arg	missense_variant	7/10	1	NM_006833.5	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.47	T;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.082
Sift	Benign	0.033	D;D
Sift4G	Benign	0.27	T;T
Polyphen		0.30	B;.
Vest4		0.30
MutPred		0.28		Loss of glycosylation at S211 (P = 0.003);.;
MVP		0.48
MPC		1.1
ClinPred		0.95	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.74
gMVP		0.41

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: rs193921011; hg19: chr7-99688757; COSMIC: COSV57994983; COSMIC: COSV57994983;