NM_005299.3:c.946G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005299.3(GPR31):​c.946G>A​(p.Asp316Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,600,790 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

GPR31
NM_005299.3 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.830
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]

Genome browser will be placed here

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=0.0846709).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPR31NM_005299.3 linkc.946G>A p.Asp316Asn 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.946G>A p.Asp316Asn missense_variant Exon 1 of 1 6 NM_005299.3 ENSP00000355799.2 O00270
ENSG00000291286ENST00000486697.2 linkn.122+6813C>T intron_variant Intron 2 of 3 5
ENSG00000291286ENST00000539001.6 linkn.368+7402C>T intron_variant Intron 2 of 4 5

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152148
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000414
AC:
1
AN:
241732
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
130524
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000910
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000159
AC:
23
AN:
1448642
Hom.:
0
Cov.:
30
AF XY:
0.0000139
AC XY:
10
AN XY:
719494
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:
0.0000199
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152148
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000315
Hom.:
0
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 22, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.946G>A (p.D316N) alteration is located in exon 1 (coding exon 1) of the GPR31 gene. This alteration results from a G to A substitution at nucleotide position 946, causing the aspartic acid (D) at amino acid position 316 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.017
T
Eigen
Benign
-0.87
Eigen_PC
Benign
-0.91
FATHMM_MKL
Benign
0.041
N
LIST_S2
Benign
0.42
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.085
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.90
L
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-1.0
N
REVEL
Benign
0.042
Sift
Benign
0.18
T
Sift4G
Pathogenic
0.0
D
Polyphen
0.33
B
Vest4
0.23
MutPred
0.17
Gain of catalytic residue at D316 (P = 0.0221);
MVP
0.50
MPC
0.15
ClinPred
0.14
T
GERP RS
2.6
Varity_R
0.10
gMVP
0.096

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs780218828; hg19: chr6-167570374; API