2-132417070-G-C

Position:

• chr2-132417070-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000329321.4(GPR39):​c.28G>C​(p.Asp10His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GPR39 ENST00000329321.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.89

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]

LOC124905948 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21787849).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR39	NM_001508.3	c.28G>C	p.Asp10His	missense_variant	1/2	ENST00000329321.4	NP_001499.1
LOC124905948	XM_047446885.1			upstream_gene_variant			XP_047302841.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR39	ENST00000329321.4	c.28G>C	p.Asp10His	missense_variant	1/2	1	NM_001508.3	ENSP00000327417	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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

Aug 26, 2022

The c.28G>C (p.D10H) alteration is located in exon 1 (coding exon 1) of the GPR39 gene. This alteration results from a G to C substitution at nucleotide position 28, causing the aspartic acid (D) at amino acid position 10 to be replaced by a histidine (H). 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	0.10
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.54	T;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.4	M;.
MutationTaster	Benign	0.99	N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.8	N;.
REVEL	Benign	0.11
Sift	Uncertain	0.015	D;.
Sift4G	Uncertain	0.011	D;D
Polyphen		0.88	P;.
Vest4		0.19
MutPred		0.34		Gain of disorder (P = 0.1001);Gain of disorder (P = 0.1001);
MVP		0.79
MPC		0.75
ClinPred		0.72	D
GERP RS		2.5
Varity_R		0.077
gMVP		0.63

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: chr2-133174643;