6-167157225-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_005299.3(GPR31):​c.607G>A​(p.Ala203Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GPR31
NM_005299.3 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.693
Variant links:
Genes affected
GPR31 (HGNC:4486): (G protein-coupled receptor 31) Enables G protein-coupled receptor activity and arachidonic acid binding activity. Involved in G protein-coupled receptor signaling pathway and response to acidic pH. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.08076969).
BP6
Variant 6-167157225-C-T is Benign according to our data. Variant chr6-167157225-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3855307.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPR31NM_005299.3 linkc.607G>A p.Ala203Thr missense_variant Exon 1 of 1 ENST00000366834.2 NP_005290.2 O00270

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GPR31ENST00000366834.2 linkc.607G>A p.Ala203Thr missense_variant Exon 1 of 1 6 NM_005299.3 ENSP00000355799.2 O00270
ENSG00000291286ENST00000486697.2 linkn.122+7152C>T intron_variant Intron 2 of 3 5
ENSG00000291286ENST00000539001.6 linkn.369-7176C>T intron_variant Intron 2 of 4 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461882
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727244
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Mar 05, 2025
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.090
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
3.1
DANN
Benign
0.84
DEOGEN2
Benign
0.012
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.0063
N
LIST_S2
Benign
0.42
T
M_CAP
Benign
0.0017
T
MetaRNN
Benign
0.081
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-1.0
N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
1.6
N
REVEL
Benign
0.033
Sift
Benign
0.72
T
Sift4G
Benign
1.0
T
Polyphen
0.0010
B
Vest4
0.041
MutPred
0.60
Gain of MoRF binding (P = 0.1353);
MVP
0.19
MPC
0.10
ClinPred
0.058
T
GERP RS
-0.049
Varity_R
0.071
gMVP
0.056

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr6-167570713; COSMIC: COSV64762044; API