Genetic Variant GPR162:p.Asp358Asn (chr12-6826210-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_019858.2(GPR162):c.1072G>A(p.Asp358Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000477 in 1,613,672 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D358G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

GPR162
NM_019858.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.96

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30956239).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR162	NM_019858.2 link	c.1072G>A	p.Asp358Asn	missense_variant	Exon 4 of 5	ENST00000311268.8	NP_062832.1	Q16538-1A0A0I9QPQ8
GPR162	NM_014449.2 link	c.220G>A	p.Asp74Asn	missense_variant	Exon 4 of 5		NP_055264.1	Q16538-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GPR162	ENST00000311268.8 link	c.1072G>A	p.Asp358Asn	missense_variant	Exon 4 of 5	1	NM_019858.2	ENSP00000311528.3	Q16538-1
GPR162	ENST00000428545.6 link	c.220G>A	p.Asp74Asn	missense_variant	Exon 4 of 5	1		ENSP00000399670.2	Q16538-2
GPR162	ENST00000382315.7 link	c.160G>A	p.Asp54Asn	missense_variant	Exon 3 of 4	1		ENSP00000371752.3	J3KPJ9
GPR162	ENST00000545321.1 link	c.424G>A	p.Asp142Asn	missense_variant	Exon 3 of 4	2		ENSP00000475912.1	U3KQI6

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000482

AC:

AN:

248734

AF XY:

0.0000520

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000719

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000472

AC:

AN:

1461522

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

727070

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33474

American (AMR)

AF:

0.0000224

AC:

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.000151

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0000279

AC:

AN:

1111796

Other (OTH)

AF:

0.000497

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41432

American (AMR)

AF:

0.0000655

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68032

Other (OTH)

AF:

0.000479

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.569

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000107

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000577

AC:

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 23, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1072G>A (p.D358N) alteration is located in exon 4 (coding exon 3) of the GPR162 gene. This alteration results from a G to A substitution at nucleotide position 1072, causing the aspartic acid (D) at amino acid position 358 to be replaced by an asparagine (N). 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

0.13

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.51

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

T;.;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.31

T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.1

M;.;.

PhyloP100

5.0

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.58

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.12

T;T;T

Sift4G

Benign

0.25

T;T;T

Polyphen

1.0

D;D;.

Vest4

0.50

MVP

0.75

MPC

0.064

ClinPred

0.26

GERP RS

4.6

Varity_R

0.093

gMVP

0.56

Mutation Taster

=62/38

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

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chr12-6826210-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over