2-132417338-T-C

Position:

• chr2-132417338-T-C

Variant summary

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

The NM_001508.3(GPR39):​c.296T>C​(p.Leu99Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GPR39 NM_001508.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.59

Genes affected

GPR39 (HGNC:4496): (G protein-coupled receptor 39) This gene is a member of the ghrelin receptor family and encodes a rhodopsin-type G-protein-coupled receptor (GPCR). The encoded protein is involved in zinc-dependent signaling in epithelial tissue in intestines, prostate and salivary glands. The protein may also be involved in the pathophysiology of depression. [provided by RefSeq, Jun 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/exons	MANE	Protein	UniProt
GPR39	NM_001508.3	c.296T>C	p.Leu99Pro	missense_variant	1/2	ENST00000329321.4	NP_001499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR39	ENST00000329321.4	c.296T>C	p.Leu99Pro	missense_variant	1/2	1	NM_001508.3	ENSP00000327417.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 33

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

Sep 26, 2024

The c.296T>C (p.L99P) alteration is located in exon 1 (coding exon 1) of the GPR39 gene. This alteration results from a T to C substitution at nucleotide position 296, causing the leucine (L) at amino acid position 99 to be replaced by a proline (P). 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	Uncertain	0.41
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;.
Eigen	Benign	0.18
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.64	T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Benign	-0.40	T
MutationAssessor	Uncertain	2.0	M;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.9	N;.
REVEL	Uncertain	0.52
Sift	Benign	0.064	T;.
Sift4G	Uncertain	0.0070	D;D
Polyphen		1.0	D;.
Vest4		0.47
MutPred		0.64		Gain of glycosylation at L99 (P = 0.0155);Gain of glycosylation at L99 (P = 0.0155);
MVP		0.87
MPC		1.3
ClinPred		0.93	D
GERP RS		4.0
Varity_R		0.28
gMVP		0.80

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: chr2-133174911;