19-50771138-C-T

Variant summary

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

The NM_001506.2(GPR32):​c.538C>T​(p.Arg180Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R180Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

GPR32
NM_001506.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.144
Variant links:
Genes affected
GPR32 (HGNC:4487): (G protein-coupled receptor 32) This gene is intronless and encodes a member of the G-protein coupled receptor 1 family. The encoded protein binds to resolvin D1 and lipoxin A4 and has been linked to pulmonary inflammation. A related pseudogene has been identified on chromosome 19. [provided by RefSeq, Nov 2012]

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=0.09512773).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPR32NM_001506.2 linkc.538C>T p.Arg180Trp missense_variant Exon 1 of 1 ENST00000270590.4 NP_001497.1 O75388H9NIL6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GPR32ENST00000270590.4 linkc.538C>T p.Arg180Trp missense_variant Exon 1 of 1 6 NM_001506.2 ENSP00000270590.3 O75388

Frequencies

GnomAD3 genomes
AF:
0.000184
AC:
28
AN:
152180
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000720
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:
0.000147
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.0000835
AC:
21
AN:
251402
Hom.:
0
AF XY:
0.0000809
AC XY:
11
AN XY:
135890
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.000202
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:
0.000106
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000458
AC:
67
AN:
1461878
Hom.:
0
Cov.:
33
AF XY:
0.0000619
AC XY:
45
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000179
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:
0.0000495
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.000184
AC:
28
AN:
152180
Hom.:
0
Cov.:
31
AF XY:
0.000215
AC XY:
16
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.000720
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.000955
Alfa
AF:
0.00859
Hom.:
759
Bravo
AF:
0.000170
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 19, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.538C>T (p.R180W) alteration is located in exon 1 (coding exon 1) of the GPR32 gene. This alteration results from a C to T substitution at nucleotide position 538, causing the arginine (R) at amino acid position 180 to be replaced by a tryptophan (W). 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
0.33
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
13
DANN
Uncertain
0.99
DEOGEN2
Benign
0.095
T
Eigen
Benign
-0.95
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.071
N
LIST_S2
Benign
0.50
T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.095
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.4
M
PrimateAI
Benign
0.23
T
PROVEAN
Uncertain
-3.7
D
REVEL
Benign
0.027
Sift
Benign
0.20
T
Sift4G
Benign
0.10
T
Polyphen
0.11
B
Vest4
0.23
MVP
0.52
MPC
0.67
ClinPred
0.046
T
GERP RS
0.28
Varity_R
0.090
gMVP
0.44

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: rs142063556; hg19: chr19-51274395; COSMIC: COSV54515011; API