chr2-240630304-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005301.5(GPR35):c.352G>A(p.Val118Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000348 in 1,580,252 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000030 ( 0 hom. )
Consequence
GPR35
NM_005301.5 missense
NM_005301.5 missense
Scores
11
8
Clinical Significance
Conservation
PhyloP100: 0.422
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 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 | c.352G>A | p.Val118Met | missense_variant | 2/2 | ENST00000407714.2 | NP_005292.2 | |
GPR35 | NM_001195381.3 | c.445G>A | p.Val149Met | missense_variant | 6/6 | NP_001182310.1 | ||
GPR35 | NM_001195382.3 | c.445G>A | p.Val149Met | missense_variant | 6/6 | NP_001182311.1 | ||
GPR35 | NM_001394730.1 | c.445G>A | p.Val149Met | missense_variant | 6/6 | NP_001381659.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GPR35 | ENST00000407714.2 | c.352G>A | p.Val118Met | missense_variant | 2/2 | 1 | NM_005301.5 | ENSP00000384263.1 |
Frequencies
GnomAD3 genomes AF: 0.0000788 AC: 12AN: 152236Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000273 AC: 6AN: 219728Hom.: 0 AF XY: 0.0000250 AC XY: 3AN XY: 119968
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GnomAD4 exome AF: 0.0000301 AC: 43AN: 1428016Hom.: 0 Cov.: 38 AF XY: 0.0000353 AC XY: 25AN XY: 707746
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GnomAD4 genome AF: 0.0000788 AC: 12AN: 152236Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7AN XY: 74366
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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 | Sep 14, 2022 | The c.445G>A (p.V149M) alteration is located in exon 6 (coding exon 2) of the GPR35 gene. This alteration results from a G to A substitution at nucleotide position 445, causing the valine (V) at amino acid position 149 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;.;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
.;.;T;.;T
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;.;M;M
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;.
REVEL
Uncertain
Sift
Uncertain
D;D;T;D;.
Sift4G
Uncertain
D;D;D;D;D
Polyphen
D;D;.;D;D
Vest4
MutPred
Gain of MoRF binding (P = 0.086);Gain of MoRF binding (P = 0.086);.;Gain of MoRF binding (P = 0.086);Gain of MoRF binding (P = 0.086);
MVP
MPC
0.90
ClinPred
D
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