2-132417647-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001508.3(GPR39):​c.605C>T​(p.Pro202Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

GPR39
NM_001508.3 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.50
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.32382357).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GPR39NM_001508.3 linkuse as main transcriptc.605C>T p.Pro202Leu missense_variant 1/2 ENST00000329321.4 NP_001499.1 O43194

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GPR39ENST00000329321.4 linkuse as main transcriptc.605C>T p.Pro202Leu missense_variant 1/21 NM_001508.3 ENSP00000327417.3 O43194

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461882
Hom.:
0
Cov.:
34
AF XY:
0.00000550
AC XY:
4
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 12, 2024The c.605C>T (p.P202L) alteration is located in exon 1 (coding exon 1) of the GPR39 gene. This alteration results from a C to T substitution at nucleotide position 605, causing the proline (P) at amino acid position 202 to be replaced by a leucine (L). 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
0.079
BayesDel_addAF
Benign
-0.013
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
T;.
Eigen
Uncertain
0.23
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.75
T;T
M_CAP
Benign
0.027
D
MetaRNN
Benign
0.32
T;T
MetaSVM
Benign
-0.65
T
MutationAssessor
Uncertain
2.1
M;.
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-1.5
N;.
REVEL
Benign
0.23
Sift
Uncertain
0.0090
D;.
Sift4G
Uncertain
0.016
D;D
Polyphen
0.75
P;.
Vest4
0.75
MutPred
0.52
Loss of disorder (P = 0.0704);Loss of disorder (P = 0.0704);
MVP
0.83
MPC
0.45
ClinPred
0.94
D
GERP RS
4.9
Varity_R
0.089
gMVP
0.72

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1679932534; hg19: chr2-133175220; API