14-91234584-A-T

Position:

• chr14-91234584-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001177676.2(GPR68):​c.467T>A​(p.Phe156Tyr) 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 benign 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.50

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]

ACMG classification

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=0.39517656).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR68	NM_001177676.2	c.467T>A	p.Phe156Tyr	missense_variant	2/2	ENST00000650645.1	NP_001171147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR68	ENST00000650645.1	c.467T>A	p.Phe156Tyr	missense_variant	2/2		NM_001177676.2	ENSP00000498702	P1
GPR68	ENST00000531499.2	c.467T>A	p.Phe156Tyr	missense_variant	2/2	1		ENSP00000434045	P1
GPR68	ENST00000535815.5	c.467T>A	p.Phe156Tyr	missense_variant	2/2	1		ENSP00000440797	P1
GPR68	ENST00000529102.1	c.467T>A	p.Phe156Tyr	missense_variant	2/2	1		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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.467T>A (p.F156Y) alteration is located in exon 2 (coding exon 1) of the GPR68 gene. This alteration results from a T to A substitution at nucleotide position 467, causing the phenylalanine (F) at amino acid position 156 to be replaced by a tyrosine (Y). 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	0.37
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;T;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.61	.;T;T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.22
Sift	Uncertain	0.024	D;D;D
Sift4G	Benign	1.0	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.28
MutPred		0.45		Gain of catalytic residue at I154 (P = 0.0032);Gain of catalytic residue at I154 (P = 0.0032);Gain of catalytic residue at I154 (P = 0.0032);
MVP		0.35
MPC		1.9
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.48

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: chr14-91700928;