Variant 12-12662390-A-G 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_006143.3(GPR19):c.59T>C(p.Leu20Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GPR19
NM_006143.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20397094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR19	NM_006143.3 linkuse as main transcript	c.59T>C	p.Leu20Pro	missense_variant	4/4	ENST00000651487.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GPR19	ENST00000651487.1 linkuse as main transcript	c.59T>C	p.Leu20Pro	missense_variant	4/4		NM_006143.3	P1
GPR19	ENST00000332427.6 linkuse as main transcript	c.59T>C	p.Leu20Pro	missense_variant	4/4	4		P1
GPR19	ENST00000540510.1 linkuse as main transcript	c.59T>C	p.Leu20Pro	missense_variant	2/2	2		P1
GPR19	ENST00000540796.5 linkuse as main transcript	c.59T>C	p.Leu20Pro	missense_variant	4/4	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251482

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Dec 20, 2023

The c.59T>C (p.L20P) alteration is located in exon 4 (coding exon 1) of the GPR19 gene. This alteration results from a T to C substitution at nucleotide position 59, causing the leucine (L) at amino acid position 20 to be replaced by a proline (P). 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

0.071

BayesDel_addAF

Benign

0.011

BayesDel_noAF

Benign

-0.22

Cadd

Benign

Dann

Benign

0.92

DEOGEN2

Benign

0.10

T;T;.

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.44

FATHMM_MKL

Uncertain

0.76

M_CAP

Benign

0.020

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.0

L;L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.2

N;N;D

REVEL

Benign

0.25

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.010

D;D;.

Polyphen

0.0010

B;B;.

Vest4

0.29

MutPred

0.62

Gain of disorder (P = 0.0189);Gain of disorder (P = 0.0189);Gain of disorder (P = 0.0189);

MVP

0.35

MPC

0.64

ClinPred

0.27

GERP RS

1.9

Varity_R

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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