chrX-130384522-G-A

Position:

• chrX-130384522-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.225

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 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	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	c.926C>T	p.Ser309Leu	missense_variant	1/2		NM_178471.3	P1
GPR119	ENST00000276218.4	c.926C>T	p.Ser309Leu	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes AF: 0.00736 AC: 826 AN: 112242 Hom.: 10 Cov.: 23 AF XY: 0.00529 AC XY: 182 AN XY: 34412

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.: 1 AF XY: 0.00127 AC XY: 86 AN XY: 67673

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.: 8 Cov.: 31 AF XY: 0.000618 AC XY: 224 AN XY: 362645

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.: 10 Cov.: 23 AF XY: 0.00542 AC XY: 187 AN XY: 34476

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.: 35

Bravo AF: 0.00882

ESP6500AA AF: 0.0227 AC: 87

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00218 AC: 265

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.64
DEOGEN2	Benign	0.037	T
FATHMM_MKL	Benign	0.0089	N
LIST_S2	Benign	0.44	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.034
Sift	Benign	0.10	T
Sift4G	Benign	0.19	T
Polyphen		0.0	B
Vest4		0.087
MVP		0.83
MPC		0.44
ClinPred		0.00095	T
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

Other links and lift over

dbSNP: rs5975187; hg19: chrX-129518496;