Variant 12-6826777-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_019858.2(GPR162):c.1340G>A(p.Arg447Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000273 in 1,608,672 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 1 hom. )

Consequence

GPR162
NM_019858.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.07

Variant links:

Genes affected

GPR162 (HGNC:16693): (G protein-coupled receptor 162) This gene was identified upon genomic analysis of a gene-dense region at human chromosome 12p13. It appears to be mainly expressed in the brain; however, its function is not known. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

GPR162 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05029866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR162	NM_019858.2 linkuse as main transcript	c.1340G>A	p.Arg447Gln	missense_variant	5/5	ENST00000311268.8
GPR162	NM_014449.2 linkuse as main transcript	c.488G>A	p.Arg163Gln	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR162	ENST00000311268.8 linkuse as main transcript	c.1340G>A	p.Arg447Gln	missense_variant	5/5	1	NM_019858.2	P1	Q16538-1

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000386

AC:

AN:

245904

Hom.:

AF XY:

0.000316

AC XY:

AN XY:

133002

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000148

Gnomad ASJ exome

AF:

0.000210

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000336

Gnomad FIN exome

AF:

0.000796

Gnomad NFE exome

AF:

0.000602

Gnomad OTH exome

AF:

0.000505

GnomAD4 exome

AF:

0.000282

AC:

410

AN:

1456332

Hom.:

Cov.:

AF XY:

0.000250

AC XY:

181

AN XY:

724178

show subpopulations

Gnomad4 AFR exome

AF:

0.0000901

Gnomad4 AMR exome

AF:

0.000205

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.000997

Gnomad4 NFE exome

AF:

0.000291

Gnomad4 OTH exome

AF:

0.000316

GnomAD4 genome

AF:

0.000190

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000200

Hom.:

Bravo

AF:

0.000174

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000420

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

Aug 04, 2021

The c.1340G>A (p.R447Q) alteration is located in exon 5 (coding exon 4) of the GPR162 gene. This alteration results from a G to A substitution at nucleotide position 1340, causing the arginine (R) at amino acid position 447 to be replaced by a glutamine (Q). 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

0.077

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.52

Cadd

Benign

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.013

T;.;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.77

T;T;T

M_CAP

Benign

0.0088

MetaRNN

Benign

0.050

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.6

L;.;.

MutationTaster

Benign

0.85

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.15

N;N;N

REVEL

Benign

0.032

Sift

Uncertain

0.013

D;D;D

Sift4G

Benign

0.34

T;T;T

Polyphen

0.0070

B;B;.

Vest4

0.13

MVP

0.61

MPC

0.010

ClinPred

0.033

GERP RS

2.8

Varity_R

0.069

gMVP

0.58

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