Variant chr2-240630286-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005301.5(GPR35):c.334G>A(p.Val112Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000606 in 1,567,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

GPR35
NM_005301.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.369

Variant links:

Genes affected

GPR35 (HGNC:4492): (G protein-coupled receptor 35) Enables C-X-C chemokine receptor activity. Involved in several processes, including chemokine-mediated signaling pathway; negative regulation of voltage-gated calcium channel activity; and positive regulation of cytosolic calcium ion concentration. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

GPR35 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.025202334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR35	NM_005301.5 linkuse as main transcript	c.334G>A	p.Val112Met	missense_variant	2/2	ENST00000407714.2	NP_005292.2	Q9HC97-1B2RA17A8K2J1
GPR35	NM_001195381.3 linkuse as main transcript	c.427G>A	p.Val143Met	missense_variant	6/6		NP_001182310.1	Q9HC97-2
GPR35	NM_001195382.3 linkuse as main transcript	c.427G>A	p.Val143Met	missense_variant	6/6		NP_001182311.1	Q9HC97-2A8K2J1
GPR35	NM_001394730.1 linkuse as main transcript	c.427G>A	p.Val143Met	missense_variant	6/6		NP_001381659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR35	ENST00000407714.2 linkuse as main transcript	c.334G>A	p.Val112Met	missense_variant	2/2	1	NM_005301.5	ENSP00000384263.1		Q9HC97-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000173

AC:

AN:

213570

Hom.:

AF XY:

0.000164

AC XY:

AN XY:

115828

show subpopulations

Gnomad AFR exome

AF:

0.0000651

Gnomad AMR exome

AF:

0.0000921

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00151

Gnomad SAS exome

AF:

0.000202

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000101

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000558

AC:

AN:

1415452

Hom.:

Cov.:

AF XY:

0.0000614

AC XY:

AN XY:

699762

show subpopulations

Gnomad4 AFR exome

AF:

0.0000609

Gnomad4 AMR exome

AF:

0.0000703

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00110

Gnomad4 SAS exome

AF:

0.000297

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000549

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

AF:

0.000105

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000342

Hom.:

Bravo

AF:

0.000110

ExAC

AF:

0.000182

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 23, 2021

The c.427G>A (p.V143M) alteration is located in exon 6 (coding exon 2) of the GPR35 gene. This alteration results from a G to A substitution at nucleotide position 427, causing the valine (V) at amino acid position 143 to be replaced by a methionine (M). 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

0.21

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

T;T;.;T;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.71

.;.;T;.;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.025

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.3

M;M;.;M;M

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.9

N;N;.;N;.

REVEL

Benign

0.093

Sift

Benign

0.072

T;T;.;T;.

Sift4G

Benign

0.10

T;T;T;T;T

Polyphen

1.0

D;D;.;D;D

Vest4

0.083

MVP

0.21

MPC

0.76

ClinPred

0.043

GERP RS

-1.6

Varity_R

0.14

gMVP

0.44

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over