16-20031925-C-G

Variant names:

• chr16-20031925-C-G
• rs144836581
• NM_001002911.4:c.872G>C

Variant summary

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

The NM_001002911.4(GPR139):​c.872G>C​(p.Arg291Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R291Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPR139 NM_001002911.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57
• Publications: 0 publications found

Genes affected

GPR139 (HGNC:19995): (G protein-coupled receptor 139) This gene encodes a member of the rhodopsin family of G-protein-coupled receptors. The encoded protein is almost exclusively expressed in the central nervous system. L-tryptophan and L-phenylalanine may act as the physiologic ligands of the encoded protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

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_001002911.4. 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
	GPR139	NM_001002911.4	MANE Select	c.872G>C	p.Arg291Pro	missense	Exon 2 of 2	NP_001002911.1	Q6DWJ6
	GPR139	NM_001318483.1		c.593G>C	p.Arg198Pro	missense	Exon 3 of 3	NP_001305412.1	Q6DWJ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR139	ENST00000570682.2	TSL:1 MANE Select	c.872G>C	p.Arg291Pro	missense	Exon 2 of 2	ENSP00000458791.2	Q6DWJ6
	GPR139	ENST00000326571.7	TSL:1	n.*818G>C		non_coding_transcript_exon	Exon 3 of 3	ENSP00000370779.5	J3KPI8
	GPR139	ENST00000326571.7	TSL:1	n.*818G>C		3_prime_UTR	Exon 3 of 3	ENSP00000370779.5	J3KPI8

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
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.24	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.5	L
PhyloP100		7.6
PrimateAI	Pathogenic	0.81	D
Sift4G	Benign	0.18	T
Polyphen		0.097	B
Vest4		0.95
MutPred		0.64		Loss of MoRF binding (P = 0.0069)
MVP		0.84
MPC		1.4
ClinPred		0.94	D
GERP RS		5.5
Varity_R		0.74
gMVP		0.96

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

Other links and lift over

dbSNP: rs144836581; hg19: chr16-20043247;