chr12-6826235-A-G

Position:

• chr12-6826235-A-G

Variant summary

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

The NM_019858.2(GPR162):​c.1097A>G​(p.Lys366Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,776 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: GPR162 NM_019858.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.18

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR162	NM_019858.2	c.1097A>G	p.Lys366Arg	missense_variant	4/5	ENST00000311268.8	NP_062832.1
GPR162	NM_014449.2	c.245A>G	p.Lys82Arg	missense_variant	4/5		NP_055264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR162	ENST00000311268.8	c.1097A>G	p.Lys366Arg	missense_variant	4/5	1	NM_019858.2	ENSP00000311528.3
GPR162	ENST00000428545.6	c.245A>G	p.Lys82Arg	missense_variant	4/5	1		ENSP00000399670.2
GPR162	ENST00000382315.7	c.185A>G	p.Lys62Arg	missense_variant	3/4	1		ENSP00000371752.3
GPR162	ENST00000545321.1	c.449A>G	p.Lys150Arg	missense_variant	3/4	2		ENSP00000475912.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461776 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727208

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Jun 11, 2024

The c.1097A>G (p.K366R) alteration is located in exon 4 (coding exon 3) of the GPR162 gene. This alteration results from a A to G substitution at nucleotide position 1097, causing the lysine (K) at amino acid position 366 to be replaced by an arginine (R). 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	0.093
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T;.;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.80	T;D;D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.50	D;D;D
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.8	L;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.70	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.047	D;T;T
Sift4G	Benign	0.098	T;T;T
Polyphen		0.95	P;D;.
Vest4		0.54
MutPred		0.37		Gain of catalytic residue at D370 (P = 0.002);.;.;
MVP		0.82
MPC		0.016
ClinPred		0.77	D
GERP RS		4.6
Varity_R		0.094
gMVP		0.38

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: chr12-6935400;