Variant 14-91234045-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PVS1_ModerateBP6_Very_StrongBS2

The NM_001177676.2(GPR68):c.1006G>T(p.Glu336Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000867 in 1,501,992 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00094 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00086 ( 2 hom. )

Consequence

GPR68
NM_001177676.2 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.73

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 Benign. Variant got -10 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 0.0838 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

BP6

Variant 14-91234045-C-A is Benign according to our data. Variant chr14-91234045-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 728166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR68	NM_001177676.2 linkuse as main transcript	c.1006G>T	p.Glu336Ter	stop_gained	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.1006G>T	p.Glu336Ter	stop_gained	2/2		NM_001177676.2	ENSP00000498702	P1
GPR68	ENST00000531499.2 linkuse as main transcript	c.1006G>T	p.Glu336Ter	stop_gained	2/2	1		ENSP00000434045	P1
GPR68	ENST00000535815.5 linkuse as main transcript	c.1006G>T	p.Glu336Ter	stop_gained	2/2	1		ENSP00000440797	P1
GPR68	ENST00000529102.1 linkuse as main transcript	c.1006G>T	p.Glu336Ter	stop_gained	2/2	1		ENSP00000432740

Frequencies

GnomAD3 genomes

AF:

0.000939

AC:

143

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00348

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00144

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000897

AC:

AN:

104750

Hom.:

AF XY:

0.000788

AC XY:

AN XY:

54536

show subpopulations

Gnomad AFR exome

AF:

0.000563

Gnomad AMR exome

AF:

0.0000575

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00383

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.000991

GnomAD4 exome

AF:

0.000859

AC:

1159

AN:

1349632

Hom.:

Cov.:

AF XY:

0.000809

AC XY:

535

AN XY:

661628

show subpopulations

Gnomad4 AFR exome

AF:

0.000168

Gnomad4 AMR exome

AF:

0.0000364

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00356

Gnomad4 NFE exome

AF:

0.000897

Gnomad4 OTH exome

AF:

0.000755

GnomAD4 genome

AF:

0.000939

AC:

143

AN:

152360

Hom.:

Cov.:

AF XY:

0.000966

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00348

Gnomad4 NFE

AF:

0.00144

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.000691

ESP6500AA

AF:

0.000270

AC:

ESP6500EA

AF:

0.000693

AC:

ExAC

AF:

0.000366

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.52

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.88

MutationTaster

Benign

1.0

D;D;D

Vest4

0.64

GERP RS

3.1

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