chr2-132645341-A-C

Position:

chr2-132645341-A-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001508.3(GPR39):c.1097A>C(p.Gln366Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000173 in 1,614,042 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q366R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

GPR39
NM_001508.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.413

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04635805).

BP6

Variant 2-132645341-A-C is Benign according to our data. Variant chr2-132645341-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2601732.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR39	NM_001508.3 linkuse as main transcript	c.1097A>C	p.Gln366Pro	missense_variant	2/2	ENST00000329321.4
LYPD1	NM_144586.7 linkuse as main transcript	c.*704T>G		3_prime_UTR_variant	3/3	ENST00000397463.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR39	ENST00000329321.4 linkuse as main transcript	c.1097A>C	p.Gln366Pro	missense_variant	2/2	1	NM_001508.3	P1
LYPD1	ENST00000397463.3 linkuse as main transcript	c.*704T>G		3_prime_UTR_variant	3/3	1	NM_144586.7	P1	Q8N2G4-1
GPR39	ENST00000470071.1 linkuse as main transcript	n.800A>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000603

AC:

AN:

248758

Hom.:

AF XY:

0.0000668

AC XY:

AN XY:

134722

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000135

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000185

AC:

271

AN:

1461822

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

127

AN XY:

727228

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000240

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000254

Hom.:

Bravo

AF:

0.0000907

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 21, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.35

DANN

Benign

0.81

DEOGEN2

Benign

0.073

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.41

M_CAP

Benign

0.0032

MetaRNN

Benign

0.046

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.41

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.23

REVEL

Benign

0.10

Sift

Benign

0.33

Sift4G

Benign

0.21

Polyphen

0.0

Vest4

0.11

MutPred

0.53

Loss of catalytic residue at Q366 (P = 0.053);

MVP

0.17

MPC

0.39

ClinPred

0.050

GERP RS

-10

Varity_R

0.032

gMVP

0.29

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