Variant 12-12662000-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_006143.3(GPR19):c.449G>A(p.Gly150Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000889 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

GPR19
NM_006143.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.03

Variant links:

Genes affected

GPR19 (HGNC:4473): (G protein-coupled receptor 19) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in cilium. [provided by Alliance of Genome Resources, Apr 2022]

GPR19 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.842

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR19	NM_006143.3 linkuse as main transcript	c.449G>A	p.Gly150Asp	missense_variant	4/4	ENST00000651487.1	NP_006134.2	Q15760Q6IBH2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GPR19	ENST00000651487.1 linkuse as main transcript	c.449G>A	p.Gly150Asp	missense_variant	4/4		NM_006143.3	ENSP00000498976.1	Q15760
GPR19	ENST00000332427.6 linkuse as main transcript	c.449G>A	p.Gly150Asp	missense_variant	4/4	4		ENSP00000333744.2	Q15760
GPR19	ENST00000540510.1 linkuse as main transcript	c.449G>A	p.Gly150Asp	missense_variant	2/2	2		ENSP00000441832.1	Q15760

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251252

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000108

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

Jul 06, 2024

The c.449G>A (p.G150D) alteration is located in exon 4 (coding exon 1) of the GPR19 gene. This alteration results from a G to A substitution at nucleotide position 449, causing the glycine (G) at amino acid position 150 to be replaced by an aspartic acid (D). 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

Pathogenic

0.89

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

T;T

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.096

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

.;D

M_CAP

Benign

0.029

MetaRNN

Pathogenic

0.84

D;D

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.6

M;M

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.4

N;N

REVEL

Uncertain

0.45

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.037

D;D

Polyphen

1.0

D;D

Vest4

0.90

MutPred

0.66

Loss of catalytic residue at V151 (P = 0.0965);Loss of catalytic residue at V151 (P = 0.0965);

MVP

0.13

MPC

1.4

ClinPred

0.82

GERP RS

4.3

Varity_R

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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