14-91234192-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001177676.2(GPR68):​c.859T>G​(p.Cys287Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

GPR68
NM_001177676.2 missense

Scores

5
11
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.31
Variant links:
Genes affected
GPR68 (HGNC:4519): (G protein-coupled receptor 68) The protein encoded by this gene is a G protein-coupled receptor for sphingosylphosphorylcholine. The encoded protein is a proton-sensing receptor, inactive at pH 7.8 but active at pH 6.8. Mutations in this gene are a cause of amelogenesis imperfecta. [provided by RefSeq, Feb 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.837

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GPR68NM_001177676.2 linkuse as main transcriptc.859T>G p.Cys287Gly missense_variant 2/2 ENST00000650645.1 NP_001171147.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GPR68ENST00000650645.1 linkuse as main transcriptc.859T>G p.Cys287Gly missense_variant 2/2 NM_001177676.2 ENSP00000498702 P1
GPR68ENST00000531499.2 linkuse as main transcriptc.859T>G p.Cys287Gly missense_variant 2/21 ENSP00000434045 P1
GPR68ENST00000535815.5 linkuse as main transcriptc.859T>G p.Cys287Gly missense_variant 2/21 ENSP00000440797 P1
GPR68ENST00000529102.1 linkuse as main transcriptc.859T>G p.Cys287Gly missense_variant 2/21 ENSP00000432740

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
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 31, 2023The c.859T>G (p.C287G) alteration is located in exon 2 (coding exon 1) of the GPR68 gene. This alteration results from a T to G substitution at nucleotide position 859, causing the cysteine (C) at amino acid position 287 to be replaced by a glycine (G). 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
0.52
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.070
CADD
Pathogenic
28
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.47
T;T;T
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.91
.;D;D
M_CAP
Uncertain
0.093
D
MetaRNN
Pathogenic
0.84
D;D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.90
L;L;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.82
D
PROVEAN
Pathogenic
-8.4
D;D;D
REVEL
Uncertain
0.49
Sift
Pathogenic
0.0
D;D;D
Sift4G
Uncertain
0.012
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.86
MutPred
0.63
Gain of catalytic residue at E291 (P = 0.001);Gain of catalytic residue at E291 (P = 0.001);Gain of catalytic residue at E291 (P = 0.001);
MVP
0.47
MPC
1.4
ClinPred
0.99
D
GERP RS
5.3
Varity_R
0.92

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: chr14-91700536; API