X-130385078-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.849

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]

ACMG classification

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	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	c.370G>T	p.Ala124Ser	missense_variant	1/2		NM_178471.3	P1
GPR119	ENST00000276218.4	c.370G>T	p.Ala124Ser	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098102 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 363460

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.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	0.97
Dann	Benign	0.97
DEOGEN2	Benign	0.029	T
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.091
Sift	Benign	0.15	T
Sift4G	Benign	0.55	T
Polyphen		0.10	B
Vest4		0.12
MutPred		0.58		Gain of glycosylation at A124 (P = 0.0934);
MVP		0.69
MPC		0.48
ClinPred		0.078	T
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.

Other links and lift over

hg19: chrX-129519052;