Variant rs1057517671 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5

The NM_001177676.2(GPR68):c.667_668del(p.Lys223GlyfsTer113) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,441,932 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GPR68
NM_001177676.2 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:2

Conservation

PhyloP100: 8.01

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]

GPR68 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.393 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 14-91234382-CTT-C is Pathogenic according to our data. Variant chr14-91234382-CTT-C is described in ClinVar as [Pathogenic]. Clinvar id is 268085.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR68	NM_001177676.2 linkuse as main transcript	c.667_668del	p.Lys223GlyfsTer113	frameshift_variant	2/2	ENST00000650645.1	NP_001171147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
GPR68	ENST00000650645.1 linkuse as main transcript	c.667_668del	p.Lys223GlyfsTer113	frameshift_variant	2/2		NM_001177676.2	ENSP00000498702	P1
GPR68	ENST00000529102.1 linkuse as main transcript	c.667_668del	p.Lys223GlyfsTer113	frameshift_variant	2/2	1		ENSP00000432740
GPR68	ENST00000531499.2 linkuse as main transcript	c.667_668del	p.Lys223GlyfsTer113	frameshift_variant	2/2	1		ENSP00000434045	P1
GPR68	ENST00000535815.5 linkuse as main transcript	c.667_668del	p.Lys223GlyfsTer113	frameshift_variant	2/2	1		ENSP00000440797	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000470

AC:

AN:

212944

Hom.:

AF XY:

0.00000861

AC XY:

AN XY:

116182

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000359

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1441932

Hom.:

AF XY:

0.00000279

AC XY:

AN XY:

716226

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:

0.0000238

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Amelogenesis imperfecta, hypomaturation type, IIa6

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 21, 2016

- -

Amelogenesis imperfecta

Pathogenic:1

Pathogenic, no assertion criteria provided

research

Leeds Amelogenesis Imperfecta Research Group, University of Leeds

Aug 01, 2016

Predicted to remove two of the protein's transmembrane helices and two pH sensing histidine residues. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over