chr12-6825667-G-C

Position:

• chr12-6825667-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_019858.2(GPR162):​c.1051G>C​(p.Asp351His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GPR162 NM_019858.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.77

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30892217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR162	NM_019858.2	c.1051G>C	p.Asp351His	missense_variant	3/5	ENST00000311268.8	NP_062832.1
GPR162	NM_014449.2	c.199G>C	p.Asp67His	missense_variant	3/5		NP_055264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR162	ENST00000311268.8	c.1051G>C	p.Asp351His	missense_variant	3/5	1	NM_019858.2	ENSP00000311528.3
GPR162	ENST00000428545.6	c.199G>C	p.Asp67His	missense_variant	3/5	1		ENSP00000399670.2
GPR162	ENST00000382315.7	c.139G>C	p.Asp47His	missense_variant	2/4	1		ENSP00000371752.3
GPR162	ENST00000545321.1	c.403G>C	p.Asp135His	missense_variant	2/4	2		ENSP00000475912.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2023

The c.1051G>C (p.D351H) alteration is located in exon 3 (coding exon 2) of the GPR162 gene. This alteration results from a G to C substitution at nucleotide position 1051, causing the aspartic acid (D) at amino acid position 351 to be replaced by a histidine (H). 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	0.24
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	T;.;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.85	T;T;T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.1	M;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.1	N;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.98	D;P;.
Vest4		0.41
MutPred		0.47		Gain of catalytic residue at D352 (P = 5e-04);.;.;
MVP		0.83
MPC		1.5
ClinPred		0.90	D
GERP RS		4.3
Varity_R		0.21
gMVP		0.52

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-6934832;