Variant 12-6826696-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019858.2(GPR162):c.1259T>C(p.Phe420Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000793 in 1,539,014 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000076 ( 0 hom. )

Consequence

GPR162
NM_019858.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.92

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR162	NM_019858.2 linkuse as main transcript	c.1259T>C	p.Phe420Ser	missense_variant	5/5	ENST00000311268.8
GPR162	NM_014449.2 linkuse as main transcript	c.407T>C	p.Phe136Ser	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR162	ENST00000311268.8 linkuse as main transcript	c.1259T>C	p.Phe420Ser	missense_variant	5/5	1	NM_019858.2	P1	Q16538-1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000794

AC:

AN:

188818

Hom.:

AF XY:

0.0000500

AC XY:

AN XY:

99924

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000216

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000595

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000884

Gnomad OTH exome

AF:

0.000228

GnomAD4 exome

AF:

0.0000757

AC:

105

AN:

1386750

Hom.:

Cov.:

AF XY:

0.0000688

AC XY:

AN XY:

683010

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000253

Gnomad4 ASJ exome

AF:

0.0000480

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000274

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000834

Gnomad4 OTH exome

AF:

0.0000701

GnomAD4 genome

AF:

0.000112

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000907

ExAC

AF:

0.0000826

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Sep 19, 2023

The c.1259T>C (p.F420S) alteration is located in exon 5 (coding exon 4) of the GPR162 gene. This alteration results from a T to C substitution at nucleotide position 1259, causing the phenylalanine (F) at amino acid position 420 to be replaced by a serine (S). 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

Uncertain

0.42

BayesDel_addAF

Uncertain

0.050

BayesDel_noAF

Uncertain

0.13

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.036

T;.;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.77

T;T;T

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.58

D;D;D

MetaSVM

Benign

-0.63

MutationAssessor

Benign

1.5

L;.;.

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.2

N;D;D

REVEL

Uncertain

0.37

Sift

Uncertain

0.0020

D;D;D

Sift4G

Benign

0.083

T;T;T

Polyphen

0.99

D;D;.

Vest4

0.78

MVP

0.79

MPC

0.042

ClinPred

0.17

GERP RS

4.9

Varity_R

0.29

gMVP

0.55

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