16-20032217-C-T

Variant names:

• chr16-20032217-C-T
• NM_001002911.4:c.580G>A

Variant summary

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

The NM_001002911.4(GPR139):​c.580G>A​(p.Val194Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPR139 NM_001002911.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.71

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

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 rank	MANE	Protein	UniProt
GPR139	NM_001002911.4	c.580G>A	p.Val194Met	missense_variant	Exon 2 of 2	ENST00000570682.2	NP_001002911.1
GPR139	NM_001318483.1	c.301G>A	p.Val101Met	missense_variant	Exon 3 of 3		NP_001305412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR139	ENST00000570682.2	c.580G>A	p.Val194Met	missense_variant	Exon 2 of 2	1	NM_001002911.4	ENSP00000458791.2
GPR139	ENST00000326571.7	n.*526G>A		non_coding_transcript_exon_variant	Exon 3 of 3	1		ENSP00000370779.5
GPR139	ENST00000326571.7	n.*526G>A		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000370779.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.580G>A (p.V194M) alteration is located in exon 2 (coding exon 2) of the GPR139 gene. This alteration results from a G to A substitution at nucleotide position 580, causing the valine (V) at amino acid position 194 to be replaced by a methionine (M). 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	0.17
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.086	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.2	L
PrimateAI	Uncertain	0.67	T
Sift4G	Benign	0.15	T
Polyphen		0.96	D
Vest4		0.51
MutPred		0.38		Loss of stability (P = 0.0906);
MVP		0.87
MPC		0.87
ClinPred		0.95	D
GERP RS		5.7
Varity_R		0.25
gMVP		0.77

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: chr16-20043539;