dbSNP rs139420660: GPR19:p.Val155Ile (chr12-12661986-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006143.3(GPR19):c.463G>A(p.Val155Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000118 in 1,613,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

GPR19
NM_006143.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.12

Publications

0 publications found

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:

ENSG00000257004 (HGNC:):

ENSG00000257004 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10020447).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006143.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR19	NM_006143.3	MANE Select	c.463G>A	p.Val155Ile	missense	Exon 4 of 4	NP_006134.2	Q15760

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPR19	ENST00000651487.1	MANE Select	c.463G>A	p.Val155Ile	missense	Exon 4 of 4	ENSP00000498976.1	Q15760
GPR19	ENST00000332427.6	TSL:4	c.463G>A	p.Val155Ile	missense	Exon 4 of 4	ENSP00000333744.2	Q15760
GPR19	ENST00000540510.1	TSL:2	c.463G>A	p.Val155Ile	missense	Exon 2 of 2	ENSP00000441832.1	Q15760

Frequencies

GnomAD3 genomes

AF:

0.000172

AC:

AN:

151232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000730

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000835

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000243

AC:

AN:

251296

AF XY:

0.000250

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00143

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000112

AC:

164

AN:

1461854

Hom.:

Cov.:

AF XY:

0.000132

AC XY:

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.000475

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00114

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000477

AC:

AN:

1111988

Other (OTH)

AF:

0.0000828

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000172

AC:

AN:

151232

Hom.:

Cov.:

AF XY:

0.000271

AC XY:

AN XY:

73896

show subpopulations

African (AFR)

AF:

0.0000730

AC:

AN:

41068

American (AMR)

AF:

0.0000657

AC:

AN:

15212

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3454

East Asian (EAS)

AF:

0.00

AC:

AN:

5130

South Asian (SAS)

AF:

0.000835

AC:

AN:

4788

European-Finnish (FIN)

AF:

0.00151

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67696

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000654

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000181

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.090

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.0069

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.8

PhyloP100

6.1

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.76

REVEL

Benign

0.26

Sift

Benign

0.046

Sift4G

Benign

0.14

Polyphen

0.99

Vest4

0.48

MVP

0.040

MPC

0.85

ClinPred

0.094

GERP RS

5.1

Varity_R

0.53

Mutation Taster

=81/19

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over