chr1-168085566-C-A

Variant names:

• chr1-168085566-C-A
• rs754398620
• NM_001375883.1:c.1555G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001375883.1(GPR161):​c.1555G>T​(p.Glu519*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPR161 NM_001375883.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.89
• Publications: 2 publications found

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]

GPR161 Gene-Disease associations (from GenCC):

• pituitary stalk interruption syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375883.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR161	NM_001375883.1	MANE Select	c.1555G>T	p.Glu519*	stop_gained	Exon 6 of 6	NP_001362812.1	Q8N6U8-1
	GPR161	NM_001267609.1		c.1615G>T	p.Glu539*	stop_gained	Exon 7 of 7	NP_001254538.1	Q8N6U8-6
	GPR161	NM_001267611.1		c.1606G>T	p.Glu536*	stop_gained	Exon 6 of 6	NP_001254540.1	A0A0A0MQW8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR161	ENST00000682931.1	MANE Select	c.1555G>T	p.Glu519*	stop_gained	Exon 6 of 6	ENSP00000506967.1	Q8N6U8-1
	GPR161	ENST00000271357.9	TSL:1	c.1606G>T	p.Glu536*	stop_gained	Exon 6 of 6	ENSP00000271357.6	A0A0A0MQW8
	GPR161	ENST00000367838.5	TSL:1	c.1555G>T	p.Glu519*	stop_gained	Exon 8 of 8	ENSP00000356812.1	Q8N6U8-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.49	D
BayesDel_noAF	Pathogenic	0.47
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.92	D
PhyloP100		4.9
Vest4		0.15
GERP RS		2.4
Mutation Taster		=40/160	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs754398620; hg19: chr1-168054804;