Variant 14-88011233-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000267549.5(GPR65):c.386G>C(p.Arg129Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000186 in 1,613,938 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

GPR65
ENST00000267549.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.634

Variant links:

Genes affected

GPR65 (HGNC:4517): (G protein-coupled receptor 65) Enables G protein-coupled receptor activity. Involved in several processes, including actin cytoskeleton reorganization; activation of GTPase activity; and positive regulation of stress fiber assembly. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

GPR65 links:

(HGNC:):

links:

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=0.118100405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR65	NM_003608.4 linkuse as main transcript	c.386G>C	p.Arg129Thr	missense_variant	2/2	ENST00000267549.5	NP_003599.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR65	ENST00000267549.5 linkuse as main transcript	c.386G>C	p.Arg129Thr	missense_variant	2/2	1	NM_003608.4	ENSP00000267549	P1
	ENST00000554433.1 linkuse as main transcript	n.96-14C>G		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

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:

0.000235

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.0000997

AC:

AN:

250876

Hom.:

AF XY:

0.0000885

AC XY:

AN XY:

135564

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000202

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:

0.000150

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000185

AC:

271

AN:

1461658

Hom.:

Cov.:

AF XY:

0.000182

AC XY:

132

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000179

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:

0.000223

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000190

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000183

Hom.:

Bravo

AF:

0.000196

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

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

Jun 17, 2024

The c.386G>C (p.R129T) alteration is located in exon 2 (coding exon 1) of the GPR65 gene. This alteration results from a G to C substitution at nucleotide position 386, causing the arginine (R) at amino acid position 129 to be replaced by a threonine (T). 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

0.18

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Uncertain

0.44

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.79

M_CAP

Benign

0.025

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.88

MutationAssessor

Pathogenic

3.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.24

Sift

Uncertain

0.0030

Sift4G

Benign

0.22

Polyphen

0.86

Vest4

0.23

MVP

0.46

MPC

0.75

ClinPred

0.25

GERP RS

0.91

Varity_R

0.38

gMVP

0.48

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over