Variant X-130384802-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_178471.3(GPR119):c.646C>T(p.Arg216Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000165 in 1,210,116 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

GPR119
NM_178471.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00400

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR119	NM_178471.3 linkuse as main transcript	c.646C>T	p.Arg216Trp	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.646C>T	p.Arg216Trp	missense_variant	1/2		NM_178471.3	P1
GPR119	ENST00000276218.4 linkuse as main transcript	c.646C>T	p.Arg216Trp	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes

AF:

0.00000892

AC:

AN:

112083

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

34231

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1098033

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363387

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:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000892

AC:

AN:

112083

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

34231

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:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

May 20, 2024

The c.646C>T (p.R216W) alteration is located in exon 1 (coding exon 1) of the GPR119 gene. This alteration results from a C to T substitution at nucleotide position 646, causing the arginine (R) at amino acid position 216 to be replaced by a tryptophan (W). 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

0.11

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.72

M_CAP

Pathogenic

0.45

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-0.79

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.23

Sift

Uncertain

0.011

Sift4G

Uncertain

0.014

Polyphen

1.0

Vest4

0.31

MutPred

0.65

Loss of solvent accessibility (P = 0.0023);

MVP

0.80

MPC

1.4

ClinPred

0.88

GERP RS

2.1

Varity_R

0.16

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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