Variant X-130385078-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178471.3(GPR119):c.370G>T(p.Ala124Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,102 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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 Uncertain significance (★).

Frequency

Genomes: not found (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: -0.849

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1660459).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR119	NM_178471.3 linkuse as main transcript	c.370G>T	p.Ala124Ser	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.370G>T	p.Ala124Ser	missense_variant	1/2		NM_178471.3	P1
GPR119	ENST00000276218.4 linkuse as main transcript	c.370G>T	p.Ala124Ser	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1098102

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363460

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

Cov.:

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

Jun 01, 2023

The c.370G>T (p.A124S) alteration is located in exon 1 (coding exon 1) of the GPR119 gene. This alteration results from a G to T substitution at nucleotide position 370, causing the alanine (A) at amino acid position 124 to be replaced by a serine (S). 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

0.097

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.97

DANN

Benign

0.97

DEOGEN2

Benign

0.029

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.40

M_CAP

Benign

0.036

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.82

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.74

REVEL

Benign

0.091

Sift

Benign

0.15

Sift4G

Benign

0.55

Polyphen

0.10

Vest4

0.12

MutPred

0.58

Gain of glycosylation at A124 (P = 0.0934);

MVP

0.69

MPC

0.48

ClinPred

0.078

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.071

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over