2-240630275-C-G

Variant names:

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

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: 85 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005301.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR35	NM_005301.5	MANE Select	c.323C>G	p.Thr108Arg	missense	Exon 2 of 2	NP_005292.2
	GPR35	NM_001195381.3		c.416C>G	p.Thr139Arg	missense	Exon 6 of 6	NP_001182310.1	Q9HC97-2
	GPR35	NM_001195382.3		c.416C>G	p.Thr139Arg	missense	Exon 6 of 6	NP_001182311.1	Q9HC97-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR35	ENST00000407714.2	TSL:1 MANE Select	c.323C>G	p.Thr108Arg	missense	Exon 2 of 2	ENSP00000384263.1	Q9HC97-1
	GPR35	ENST00000430267.2	TSL:5	c.416C>G	p.Thr139Arg	missense	Exon 2 of 2	ENSP00000411788.2	Q9HC97-2
	GPR35	ENST00000319838.10	TSL:2	c.323C>G	p.Thr108Arg	missense	Exon 6 of 6	ENSP00000322731.5	Q9HC97-1

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 v4.9

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
Eigen	Benign	-0.64
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.62	T
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Pathogenic	3.5	H
PhyloP100		-0.80
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.37
MutPred		0.66		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;