chr1-168104804-A-G

Variant names:

• chr1-168104804-A-G
• NM_001375883.1:c.47T>C
• GPR161 p.Leu16Pro

Variant summary

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

The NM_001375883.1(GPR161):​c.47T>C​(p.Leu16Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GPR161 NM_001375883.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.41
• Publications: 0 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

ENSG00000306311 (HGNC:):

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.47T>C	p.Leu16Pro	missense	Exon 2 of 6	NP_001362812.1	Q8N6U8-1
	GPR161	NM_001267609.1		c.107T>C	p.Leu36Pro	missense	Exon 3 of 7	NP_001254538.1	Q8N6U8-6
	GPR161	NM_001267611.1		c.98T>C	p.Leu33Pro	missense	Exon 2 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.47T>C	p.Leu16Pro	missense	Exon 2 of 6	ENSP00000506967.1	Q8N6U8-1
	GPR161	ENST00000271357.9	TSL:1	c.98T>C	p.Leu33Pro	missense	Exon 2 of 6	ENSP00000271357.6	A0A0A0MQW8
	GPR161	ENST00000367838.5	TSL:1	c.47T>C	p.Leu16Pro	missense	Exon 4 of 8	ENSP00000356812.1	Q8N6U8-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		3.4
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.11
Sift	Benign	0.030	D
Sift4G	Uncertain	0.036	D
Varity_R		0.25
gMVP		0.68
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-168074042;