1-168085701-C-T

Position:

• chr1-168085701-C-T

Variant summary

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

The NM_001375883.1(GPR161):​c.1420G>A​(p.Ala474Thr) 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: 32)
• Consequence: GPR161 NM_001375883.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.43

Genes affected

GPR161 (HGNC:23694): (G protein-coupled receptor 161) The protein encoded by this gene is an orphan G protein-coupled receptor whose ligand is unknown. This gene is overexpressed in triple-negative breast cancer, and disruption of this gene slows the proliferation of basal breast cancer cells. Therefore, this gene is a potential drug target for triple-negative breast cancer. [provided by RefSeq, Mar 2017]

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=0.2694999).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR161	NM_001375883.1	c.1420G>A	p.Ala474Thr	missense_variant	6/6	ENST00000682931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR161	ENST00000682931.1	c.1420G>A	p.Ala474Thr	missense_variant	6/6		NM_001375883.1	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Jan 30, 2024

The c.1420G>A (p.A474T) alteration is located in exon 8 (coding exon 5) of the GPR161 gene. This alteration results from a G to A substitution at nucleotide position 1420, causing the alanine (A) at amino acid position 474 to be replaced by a threonine (T). 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	0.14
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Pathogenic	1.0
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	D;D;D;D;.;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.27	T;T;T;T;T;T;T
MetaSVM	Uncertain	0.24	D
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.87	N;N;N;N;N;N;N
REVEL	Benign	0.29
Sift	Uncertain	0.0020	D;D;T;D;D;D;D
Sift4G	Uncertain	0.017	D;D;D;D;D;D;D
Polyphen		0.91	.;.;.;.;P;.;P
Vest4		0.13
MutPred		0.35		.;.;.;.;Loss of helix (P = 3e-04);.;Loss of helix (P = 3e-04);
MVP		0.93
MPC		0.91
ClinPred		0.83	D
GERP RS		5.9
Varity_R		0.18
gMVP		0.54

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

Other links and lift over

dbSNP: rs1694421014; hg19: chr1-168054939;