Variant X-130384522-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_178471.3(GPR119):c.926C>T(p.Ser309Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,209,561 control chromosomes in the GnomAD database, including 18 homozygotes. There are 411 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0074 ( 10 hom., 187 hem., cov: 23)

Exomes 𝑓: 0.00079 ( 8 hom. 224 hem. )

Consequence

GPR119
NM_178471.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.225

Variant links:

Genes affected

GPR119 (HGNC:19060): (G protein-coupled receptor 119) This gene encodes a member of the rhodopsin subfamily of G-protein-coupled receptors that is expressed in the pancreas and gastrointestinal tract. The encoded protein is activated by lipid amides including lysophosphatidylcholine and oleoylethanolamide and may be involved in glucose homeostasis. This protein is a potential drug target in the treatment of type 2 diabetes.[provided by RefSeq, Jan 2010]

GPR119 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004087627).

BP6

Variant X-130384522-G-A is Benign according to our data. Variant chrX-130384522-G-A is described in ClinVar as [Benign]. Clinvar id is 780736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0074 (831/112296) while in subpopulation AFR AF= 0.0257 (794/30936). AF 95% confidence interval is 0.0242. There are 10 homozygotes in gnomad4. There are 187 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR119	NM_178471.3 linkuse as main transcript	c.926C>T	p.Ser309Leu	missense_variant	1/2	ENST00000682440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR119	ENST00000682440.1 linkuse as main transcript	c.926C>T	p.Ser309Leu	missense_variant	1/2		NM_178471.3	P1
GPR119	ENST00000276218.4 linkuse as main transcript	c.926C>T	p.Ser309Leu	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes

AF:

0.00736

AC:

826

AN:

112242

Hom.:

Cov.:

AF XY:

0.00529

AC XY:

182

AN XY:

34412

show subpopulations

Gnomad AFR

AF:

0.0256

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00245

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:

0.0000188

Gnomad OTH

AF:

0.00666

GnomAD3 exomes

AF:

0.00212

AC:

388

AN:

183163

Hom.:

AF XY:

0.00127

AC XY:

AN XY:

67673

show subpopulations

Gnomad AFR exome

AF:

0.0265

Gnomad AMR exome

AF:

0.00102

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000490

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.000788

AC:

865

AN:

1097265

Hom.:

Cov.:

AF XY:

0.000618

AC XY:

224

AN XY:

362645

show subpopulations

Gnomad4 AFR exome

AF:

0.0273

Gnomad4 AMR exome

AF:

0.00131

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0000739

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000190

Gnomad4 OTH exome

AF:

0.00158

GnomAD4 genome

AF:

0.00740

AC:

831

AN:

112296

Hom.:

Cov.:

AF XY:

0.00542

AC XY:

187

AN XY:

34476

show subpopulations

Gnomad4 AFR

AF:

0.0257

Gnomad4 AMR

AF:

0.00245

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00657

Alfa

AF:

0.00115

Hom.:

Bravo

AF:

0.00882

ESP6500AA

AF:

0.0227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00218

AC:

265

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	Jul 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.0

DANN

Benign

0.64

DEOGEN2

Benign

0.037

FATHMM_MKL

Benign

0.0089

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0041

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.90

REVEL

Benign

0.034

Sift

Benign

0.10

Sift4G

Benign

0.19

Polyphen

0.0

Vest4

0.087

MVP

0.83

MPC

0.44

ClinPred

0.00095

GERP RS

-1.2

Varity_R

0.049

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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