chr2-240630319-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005301.5(GPR35):c.367C>T(p.Arg123Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000252 in 1,589,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000026 ( 0 hom. )
Consequence
GPR35
NM_005301.5 missense
NM_005301.5 missense
Scores
1
3
14
Clinical Significance
Conservation
PhyloP100: -0.687
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.08086929).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPR35 | NM_005301.5 | c.367C>T | p.Arg123Cys | missense_variant | 2/2 | ENST00000407714.2 | |
GPR35 | NM_001195381.3 | c.460C>T | p.Arg154Cys | missense_variant | 6/6 | ||
GPR35 | NM_001195382.3 | c.460C>T | p.Arg154Cys | missense_variant | 6/6 | ||
GPR35 | NM_001394730.1 | c.460C>T | p.Arg154Cys | missense_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPR35 | ENST00000407714.2 | c.367C>T | p.Arg123Cys | missense_variant | 2/2 | 1 | NM_005301.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152228Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000575 AC: 13AN: 226184Hom.: 0 AF XY: 0.0000161 AC XY: 2AN XY: 124284
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GnomAD4 exome AF: 0.0000257 AC: 37AN: 1436950Hom.: 0 Cov.: 39 AF XY: 0.0000266 AC XY: 19AN XY: 713360
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152346Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74490
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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 19, 2022 | The c.460C>T (p.R154C) 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 460, causing the arginine (R) at amino acid position 154 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;.;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;M;M
MutationTaster
Benign
N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;.;D;.
REVEL
Benign
Sift
Benign
T;T;.;T;.
Sift4G
Benign
T;T;T;T;T
Polyphen
P;P;.;P;P
Vest4
MutPred
Loss of disorder (P = 0.0043);Loss of disorder (P = 0.0043);.;Loss of disorder (P = 0.0043);Loss of disorder (P = 0.0043);
MVP
MPC
0.45
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at