rs3749171

Variant names:

• chr2-240630275-C-G
• rs3749171
• NM_005301.5:c.323C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-240630275-C-G
• chr2-240630275-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005301.5(GPR35):​c.323C>G​(p.Thr108Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. T108M) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GPR35 NM_005301.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.797
• Publications: 84 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR35	NM_005301.5	c.323C>G	p.Thr108Arg	missense_variant	Exon 2 of 2	ENST00000407714.2	NP_005292.2
GPR35	NM_001195381.3	c.416C>G	p.Thr139Arg	missense_variant	Exon 6 of 6		NP_001182310.1
GPR35	NM_001195382.3	c.416C>G	p.Thr139Arg	missense_variant	Exon 6 of 6		NP_001182311.1
GPR35	NM_001394730.1	c.416C>G	p.Thr139Arg	missense_variant	Exon 6 of 6		NP_001381659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR35	ENST00000407714.2	c.323C>G	p.Thr108Arg	missense_variant	Exon 2 of 2	1	NM_005301.5	ENSP00000384263.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 6222

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Benign	0.00078	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.30	T;T;.;T;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.62	.;.;T;.;T
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.57	D;D;D;D;D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Pathogenic	3.5	H;H;.;H;H
PhyloP100		-0.80
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-4.3	D;D;.;D;.
REVEL	Uncertain	0.38
Sift	Uncertain	0.0040	D;D;.;D;.
Sift4G	Uncertain	0.0060	D;D;D;D;D
Polyphen		1.0	D;D;.;D;D
Vest4		0.37
MutPred		0.66		Gain of MoRF binding (P = 0.0132);Gain of MoRF binding (P = 0.0132);.;Gain of MoRF binding (P = 0.0132);Gain of MoRF binding (P = 0.0132);
MVP		0.59
MPC		1.0
ClinPred		0.69	D
GERP RS		-7.4
Varity_R		0.92
gMVP		0.85
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs3749171; hg19: chr2-241569692;