dbSNP rs146292223: COPS7A:p.Arg164His (chr12-6729410-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001164094.2(COPS7A):c.491G>A(p.Arg164His) variant causes a missense change. The variant allele was found at a frequency of 0.0000211 in 1,613,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R164L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

COPS7A
NM_001164094.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.65

Variant links:

Genes affected

COPS7A (HGNC:16758): (COP9 signalosome subunit 7A) This gene encodes a component of the COP9 signalosome, an evolutionarily conserved multi-subunit protease that regulates the activity of the ubiquitin conjugation pathway. Alternatively spliced transcript variants that encode the same protein have been described. [provided by RefSeq, Mar 2014]

COPS7A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.12464547).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COPS7A	NM_001164094.2 link	c.491G>A	p.Arg164His	missense_variant	Exon 5 of 8	ENST00000543155.6	NP_001157566.1	Q9UBW8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COPS7A	ENST00000543155.6 link	c.491G>A	p.Arg164His	missense_variant	Exon 5 of 8	1	NM_001164094.2	ENSP00000438115.1		Q9UBW8

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000717

AC:

AN:

251092

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000544

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1461744

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000577

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ExAC

AF:

0.0000659

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

T;T;T;.;T;T;T;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.75

.;.;.;T;.;T;T;T

M_CAP

Benign

0.0069

MetaRNN

Benign

0.12

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.0

L;L;L;.;L;.;L;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.1

N;N;N;N;N;N;N;N

REVEL

Benign

0.068

Sift

Benign

0.041

D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.057

T;T;T;T;T;D;T;D

Polyphen

0.18

B;B;B;D;B;.;B;.

Vest4

0.45

MutPred

0.35

Loss of MoRF binding (P = 0.0577);Loss of MoRF binding (P = 0.0577);Loss of MoRF binding (P = 0.0577);Loss of MoRF binding (P = 0.0577);Loss of MoRF binding (P = 0.0577);Loss of MoRF binding (P = 0.0577);Loss of MoRF binding (P = 0.0577);Loss of MoRF binding (P = 0.0577);

MVP

0.49

MPC

1.6

ClinPred

0.25

GERP RS

5.2

Varity_R

0.13

gMVP

0.22

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over