Variant 2-132417677-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_001508.3(GPR39):c.635A>G(p.Asn212Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00444 in 1,613,626 control chromosomes in the GnomAD database, including 269 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 143 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 126 hom. )

Consequence

GPR39
NM_001508.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.800

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

PM1

In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity GPR39_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.0016857684).

BP6

Variant 2-132417677-A-G is Benign according to our data. Variant chr2-132417677-A-G is described in ClinVar as [Benign]. Clinvar id is 786487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR39	NM_001508.3 linkuse as main transcript	c.635A>G	p.Asn212Ser	missense_variant	1/2	ENST00000329321.4	NP_001499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR39	ENST00000329321.4 linkuse as main transcript	c.635A>G	p.Asn212Ser	missense_variant	1/2	1	NM_001508.3	ENSP00000327417	P1

Frequencies

GnomAD3 genomes

AF:

0.0238

AC:

3613

AN:

151642

Hom.:

143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0819

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000835

Gnomad FIN

AF:

0.0000948

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.0240

GnomAD3 exomes

AF:

0.00610

AC:

1533

AN:

251286

Hom.:

AF XY:

0.00437

AC XY:

593

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.0808

Gnomad AMR exome

AF:

0.00448

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000308

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00243

AC:

3554

AN:

1461866

Hom.:

126

Cov.:

AF XY:

0.00209

AC XY:

1518

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0817

Gnomad4 AMR exome

AF:

0.00481

Gnomad4 ASJ exome

AF:

0.000459

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000243

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000185

Gnomad4 OTH exome

AF:

0.00555

GnomAD4 genome

AF:

0.0238

AC:

3614

AN:

151760

Hom.:

143

Cov.:

AF XY:

0.0228

AC XY:

1689

AN XY:

74144

show subpopulations

Gnomad4 AFR

AF:

0.0817

Gnomad4 AMR

AF:

0.0105

Gnomad4 ASJ

AF:

0.000866

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000627

Gnomad4 FIN

AF:

0.0000948

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.0237

Alfa

AF:

0.00421

Hom.:

Bravo

AF:

0.0266

ESP6500AA

AF:

0.0808

AC:

356

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00754

AC:

915

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.50

DEOGEN2

Benign

0.047

T;.

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.83

T;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.12

N;.

MutationTaster

Benign

0.70

PrimateAI

Benign

0.33

PROVEAN

Benign

0.44

N;.

REVEL

Benign

0.074

Sift

Benign

0.95

T;.

Sift4G

Benign

0.55

T;T

Polyphen

0.039

B;.

Vest4

0.088

MVP

0.51

MPC

0.26

ClinPred

0.0094

GERP RS

1.2

Varity_R

0.040

gMVP

0.46

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