19-45591707-C-T

Variant summary

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

The NM_005282.3(GPR4):​c.160G>A​(p.Val54Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,686 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: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

GPR4
NM_005282.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.460
Variant links:
Genes affected
GPR4 (HGNC:4497): (G protein-coupled receptor 4) Enables G protein-coupled receptor activity. Involved in several processes, including G protein-coupled receptor signaling pathway; positive regulation of Rho protein signal transduction; and response to acidic pH. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
OPA3 (HGNC:8142): (outer mitochondrial membrane lipid metabolism regulator OPA3) The mouse ortholog of this protein co-purifies with the mitochondrial inner membrane. Mutations in this gene have been shown to result in 3-methylglutaconic aciduria type III and autosomal dominant optic atrophy and cataract. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

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=0.11348963).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPR4NM_005282.3 linkc.160G>A p.Val54Ile missense_variant Exon 2 of 2 ENST00000323040.5 NP_005273.1 P46093

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GPR4ENST00000323040.5 linkc.160G>A p.Val54Ile missense_variant Exon 2 of 2 1 NM_005282.3 ENSP00000319744.3 P46093
OPA3ENST00000544371.1 linkc.-18+10388G>A intron_variant Intron 1 of 1 2 ENSP00000442839.1 B4DK77

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250928
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135634
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:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461686
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
727124
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 16, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.160G>A (p.V54I) alteration is located in exon 2 (coding exon 1) of the GPR4 gene. This alteration results from a G to A substitution at nucleotide position 160, causing the valine (V) at amino acid position 54 to be replaced by an isoleucine (I). 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
0.070
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
17
DANN
Benign
0.97
DEOGEN2
Benign
0.11
T
Eigen
Benign
0.0055
Eigen_PC
Benign
0.11
FATHMM_MKL
Benign
0.47
N
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-0.72
T
MutationAssessor
Benign
0.060
N
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.20
N
REVEL
Benign
0.21
Sift
Benign
0.78
T
Sift4G
Benign
0.60
T
Polyphen
0.94
P
Vest4
0.038
MutPred
0.54
Gain of catalytic residue at L59 (P = 0.0936);
MVP
0.74
MPC
0.79
ClinPred
0.43
T
GERP RS
5.1
Varity_R
0.10
gMVP
0.37

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

LitVar

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

Other links and lift over

dbSNP: rs753457588; hg19: chr19-46094965; API