Variant 2-240630152-T-C 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.200T>C(p.Leu67Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000622 in 1,447,462 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

GPR35
NM_005301.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.808

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.200T>C	p.Leu67Pro	missense_variant	2/2	ENST00000407714.2	NP_005292.2	Q9HC97-1B2RA17A8K2J1
GPR35	NM_001195381.3 linkuse as main transcript	c.293T>C	p.Leu98Pro	missense_variant	6/6		NP_001182310.1	Q9HC97-2
GPR35	NM_001195382.3 linkuse as main transcript	c.293T>C	p.Leu98Pro	missense_variant	6/6		NP_001182311.1	Q9HC97-2A8K2J1
GPR35	NM_001394730.1 linkuse as main transcript	c.293T>C	p.Leu98Pro	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.200T>C	p.Leu67Pro	missense_variant	2/2	1	NM_005301.5	ENSP00000384263.1		Q9HC97-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000330

AC:

AN:

242356

Hom.:

AF XY:

0.0000455

AC XY:

AN XY:

131752

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.00000622

AC:

AN:

1447462

Hom.:

Cov.:

AF XY:

0.00000695

AC XY:

AN XY:

719658

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jan 23, 2023

The c.293T>C (p.L98P) alteration is located in exon 6 (coding exon 2) of the GPR35 gene. This alteration results from a T to C substitution at nucleotide position 293, causing the leucine (L) at amino acid position 98 to be replaced by a proline (P). 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

Pathogenic

0.95

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

T;T;.;T;T

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.0018

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.57

.;.;T;.;T

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.70

D;D;D;D;D

MetaSVM

Benign

-0.42

MutationAssessor

Pathogenic

3.5

H;H;.;H;H

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.4

D;D;.;D;D

REVEL

Uncertain

0.35

Sift

Benign

0.12

T;T;.;T;D

Sift4G

Benign

0.16

T;T;T;T;T

Polyphen

0.99

D;D;.;D;D

Vest4

0.57

MutPred

0.68

Gain of catalytic residue at L67 (P = 0.0144);Gain of catalytic residue at L67 (P = 0.0144);.;Gain of catalytic residue at L67 (P = 0.0144);Gain of catalytic residue at L67 (P = 0.0144);

MVP

0.64

MPC

1.2

ClinPred

0.68

GERP RS

3.9

Varity_R

0.94

gMVP

0.77

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