Variant 12-6826197-T-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_019858.2(GPR162):c.1059T>G(p.Asp353Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,460,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/25 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

GPR162
NM_019858.2 missense, splice_region

Scores

Splicing: ADA: 0.00002831

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.121

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18953738).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR162	NM_019858.2 linkuse as main transcript	c.1059T>G	p.Asp353Glu	missense_variant, splice_region_variant	4/5	ENST00000311268.8	NP_062832.1	Q16538-1A0A0I9QPQ8
GPR162	NM_014449.2 linkuse as main transcript	c.207T>G	p.Asp69Glu	missense_variant, splice_region_variant	4/5		NP_055264.1	Q16538-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GPR162	ENST00000311268.8 linkuse as main transcript	c.1059T>G	p.Asp353Glu	missense_variant, splice_region_variant	4/5	1	NM_019858.2	ENSP00000311528.3	Q16538-1
GPR162	ENST00000428545.6 linkuse as main transcript	c.207T>G	p.Asp69Glu	missense_variant, splice_region_variant	4/5	1		ENSP00000399670.2	Q16538-2
GPR162	ENST00000382315.7 linkuse as main transcript	c.147T>G	p.Asp49Glu	missense_variant, splice_region_variant	3/4	1		ENSP00000371752.3	J3KPJ9
GPR162	ENST00000545321.1 linkuse as main transcript	c.411T>G	p.Asp137Glu	missense_variant, splice_region_variant	3/4	2		ENSP00000475912.1	U3KQI6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1460788

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

726678

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:

0.0000225

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000370

Hom.:

Bravo

AF:

0.00000378

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

Nov 21, 2024

The c.1059T>G (p.D353E) alteration is located in exon 4 (coding exon 3) of the GPR162 gene. This alteration results from a T to G substitution at nucleotide position 1059, causing the aspartic acid (D) at amino acid position 353 to be replaced by a glutamic acid (E). 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

0.088

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

T;.;.

Eigen

Benign

-0.095

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.66

T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.2

L;.;.

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.050

N;N;N

REVEL

Benign

0.14

Sift

Benign

0.47

T;T;T

Sift4G

Benign

0.30

T;D;D

Polyphen

0.95

P;D;.

Vest4

0.35

MutPred

0.28

Gain of solvent accessibility (P = 0.0306);.;.;

MVP

0.72

MPC

0.89

ClinPred

0.33

GERP RS

-0.98

Varity_R

0.046

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000028

dbscSNV1_RF

Benign

0.074

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: 1

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