rs548753085

Variant summary

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

The NM_005301.5(GPR35):​c.33C>A​(p.Ser11Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S11S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GPR35
NM_005301.5 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.97
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]

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=0.049705356).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPR35NM_005301.5 linkc.33C>A p.Ser11Arg missense_variant Exon 2 of 2 ENST00000407714.2 NP_005292.2 Q9HC97-1B2RA17A8K2J1
GPR35NM_001195381.3 linkc.126C>A p.Ser42Arg missense_variant Exon 6 of 6 NP_001182310.1 Q9HC97-2
GPR35NM_001195382.3 linkc.126C>A p.Ser42Arg missense_variant Exon 6 of 6 NP_001182311.1 Q9HC97-2A8K2J1
GPR35NM_001394730.1 linkc.126C>A p.Ser42Arg missense_variant Exon 6 of 6 NP_001381659.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GPR35ENST00000407714.2 linkc.33C>A p.Ser11Arg missense_variant Exon 2 of 2 1 NM_005301.5 ENSP00000384263.1 Q9HC97-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1456308
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
723520
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.02e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
0.094
DANN
Benign
0.87
DEOGEN2
Benign
0.020
T;T;.;T;T
Eigen
Benign
-2.2
Eigen_PC
Benign
-2.3
FATHMM_MKL
Benign
0.028
N
LIST_S2
Benign
0.30
.;.;T;.;T
M_CAP
Benign
0.0010
T
MetaRNN
Benign
0.050
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.55
N;N;.;N;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-1.5
N;N;.;N;.
REVEL
Benign
0.026
Sift
Benign
0.079
T;T;.;T;.
Sift4G
Benign
0.46
T;T;T;T;T
Polyphen
0.0
B;B;.;B;B
Vest4
0.15
MutPred
0.35
Loss of glycosylation at S11 (P = 0.0217);Loss of glycosylation at S11 (P = 0.0217);.;Loss of glycosylation at S11 (P = 0.0217);Loss of glycosylation at S11 (P = 0.0217);
MVP
0.12
MPC
0.31
ClinPred
0.075
T
GERP RS
-4.3
Varity_R
0.085
gMVP
0.067

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-241569402; API