2-132645376-G-A

Position:

chr2-132645376-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001508.3(GPR39):c.1132G>A(p.Ala378Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00887 in 1,613,844 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0064 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0091 ( 79 hom. )

Consequence

GPR39
NM_001508.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.256

Variant links:

Genes affected

GPR39 (HGNC:4496): (G protein-coupled receptor 39) This gene is a member of the ghrelin receptor family and encodes a rhodopsin-type G-protein-coupled receptor (GPCR). The encoded protein is involved in zinc-dependent signaling in epithelial tissue in intestines, prostate and salivary glands. The protein may also be involved in the pathophysiology of depression. [provided by RefSeq, Jun 2016]

GPR39 links:

LYPD1 (HGNC:28431): (LY6/PLAUR domain containing 1) Predicted to enable acetylcholine receptor binding activity and acetylcholine receptor inhibitor activity. Predicted to be involved in acetylcholine receptor signaling pathway. Predicted to act upstream of or within several processes, including behavioral fear response; cholinergic synaptic transmission; and negative regulation of protein localization to plasma membrane. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

LYPD1 links:

GPR39 (HGNC:):

GPR39 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032978952).

BP6

Variant 2-132645376-G-A is Benign according to our data. Variant chr2-132645376-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 218591.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR39	NM_001508.3 linkuse as main transcript	c.1132G>A	p.Ala378Thr	missense_variant	2/2	ENST00000329321.4	NP_001499.1	O43194
LYPD1	NM_144586.7 linkuse as main transcript	c.*669C>T		3_prime_UTR_variant	3/3	ENST00000397463.3	NP_653187.3	Q8N2G4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GPR39	ENST00000329321.4 linkuse as main transcript	c.1132G>A	p.Ala378Thr	missense_variant	2/2	1	NM_001508.3	ENSP00000327417.3	O43194
LYPD1	ENST00000397463 linkuse as main transcript	c.*669C>T		3_prime_UTR_variant	3/3	1	NM_144586.7	ENSP00000380605.2	Q8N2G4-1
GPR39	ENST00000470071.1 linkuse as main transcript	n.835G>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.00635

AC:

967

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00909

Gnomad ASJ

AF:

0.0297

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00876

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00679

AC:

1685

AN:

248184

Hom.:

AF XY:

0.00646

AC XY:

868

AN XY:

134458

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00663

Gnomad ASJ exome

AF:

0.0309

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00108

Gnomad FIN exome

AF:

0.00210

Gnomad NFE exome

AF:

0.00885

Gnomad OTH exome

AF:

0.0103

GnomAD4 exome

AF:

0.00913

AC:

13339

AN:

1461518

Hom.:

Cov.:

AF XY:

0.00883

AC XY:

6418

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.00143

Gnomad4 AMR exome

AF:

0.00633

Gnomad4 ASJ exome

AF:

0.0286

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000974

Gnomad4 FIN exome

AF:

0.00228

Gnomad4 NFE exome

AF:

0.0102

Gnomad4 OTH exome

AF:

0.0101

GnomAD4 genome

AF:

0.00635

AC:

968

AN:

152326

Hom.:

Cov.:

AF XY:

0.00638

AC XY:

475

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00190

Gnomad4 AMR

AF:

0.00908

Gnomad4 ASJ

AF:

0.0297

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00878

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00954

Hom.:

Bravo

AF:

0.00686

TwinsUK

AF:

0.0132

AC:

ALSPAC

AF:

0.0130

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0129

AC:

111

ExAC

AF:

0.00624

AC:

757

EpiCase

AF:

0.00943

EpiControl

AF:

0.0105

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Jun 11, 2015

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.26

DANN

Benign

0.90

DEOGEN2

Benign

0.051

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.35

MetaRNN

Benign

0.0033

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.22

PROVEAN

Benign

0.090

REVEL

Benign

0.11

Sift

Benign

0.46

Sift4G

Benign

0.56

Polyphen

0.11

Vest4

0.085

MVP

0.19

MPC

0.32

ClinPred

0.0020

GERP RS

-6.4

Varity_R

0.031

gMVP

0.18

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