Variant 2-240630140-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005301.5(GPR35):c.188C>T(p.Ala63Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000506 in 1,601,970 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

GPR35
NM_005301.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.20

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR35	NM_005301.5 linkuse as main transcript	c.188C>T	p.Ala63Val	missense_variant	2/2	ENST00000407714.2	NP_005292.2	Q9HC97-1B2RA17A8K2J1
GPR35	NM_001195381.3 linkuse as main transcript	c.281C>T	p.Ala94Val	missense_variant	6/6		NP_001182310.1	Q9HC97-2
GPR35	NM_001195382.3 linkuse as main transcript	c.281C>T	p.Ala94Val	missense_variant	6/6		NP_001182311.1	Q9HC97-2A8K2J1
GPR35	NM_001394730.1 linkuse as main transcript	c.281C>T	p.Ala94Val	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.188C>T	p.Ala63Val	missense_variant	2/2	1	NM_005301.5	ENSP00000384263.1		Q9HC97-1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000658

AC:

AN:

243120

Hom.:

AF XY:

0.0000681

AC XY:

AN XY:

132158

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000435

AC:

AN:

1449630

Hom.:

Cov.:

AF XY:

0.0000458

AC XY:

AN XY:

720982

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000387

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000118

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000551

Hom.:

Bravo

AF:

0.000128

ExAC

AF:

0.0000577

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Jul 27, 2021

The c.281C>T (p.A94V) alteration is located in exon 6 (coding exon 2) of the GPR35 gene. This alteration results from a C to T substitution at nucleotide position 281, causing the alanine (A) at amino acid position 94 to be replaced by a valine (V). 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

0.25

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

T;T;.;T;T

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.69

.;.;T;.;T

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.65

D;D;D;D;D

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.2

M;M;.;M;M

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.4

N;N;.;N;.

REVEL

Benign

0.17

Sift

Benign

0.12

T;T;.;T;.

Sift4G

Benign

0.33

T;T;T;T;T

Polyphen

0.97

D;D;.;D;D

Vest4

0.61

MVP

0.46

MPC

0.62

ClinPred

0.22

GERP RS

3.0

Varity_R

0.11

gMVP

0.47

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