Variant chr14-91234061-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001177676.2(GPR68):c.990A>T(p.Lys330Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000867 in 1,509,588 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign 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 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0100

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0063944757).

BP6

Variant 14-91234061-T-A is Benign according to our data. Variant chr14-91234061-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 728167.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.990A>T	p.Lys330Asn	missense_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.990A>T	p.Lys330Asn	missense_variant	2/2		NM_001177676.2	ENSP00000498702	P1
GPR68	ENST00000531499.2 linkuse as main transcript	c.990A>T	p.Lys330Asn	missense_variant	2/2	1		ENSP00000434045	P1
GPR68	ENST00000535815.5 linkuse as main transcript	c.990A>T	p.Lys330Asn	missense_variant	2/2	1		ENSP00000440797	P1
GPR68	ENST00000529102.1 linkuse as main transcript	c.990A>T	p.Lys330Asn	missense_variant	2/2	1		ENSP00000432740

Frequencies

GnomAD3 genomes

AF:

0.000940

AC:

143

AN:

152164

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:

0.00349

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00144

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000904

AC:

AN:

109458

Hom.:

AF XY:

0.000800

AC XY:

AN XY:

57490

show subpopulations

Gnomad AFR exome

AF:

0.000435

Gnomad AMR exome

AF:

0.0000540

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00424

Gnomad NFE exome

AF:

0.00104

Gnomad OTH exome

AF:

0.000950

GnomAD4 exome

AF:

0.000859

AC:

1166

AN:

1357306

Hom.:

Cov.:

AF XY:

0.000806

AC XY:

537

AN XY:

666138

show subpopulations

Gnomad4 AFR exome

AF:

0.000166

Gnomad4 AMR exome

AF:

0.0000342

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00367

Gnomad4 NFE exome

AF:

0.000896

Gnomad4 OTH exome

AF:

0.000750

GnomAD4 genome

AF:

0.000939

AC:

143

AN:

152282

Hom.:

Cov.:

AF XY:

0.000967

AC XY:

AN XY:

74478

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:

0.00349

Gnomad4 NFE

AF:

0.00144

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000923

Hom.:

Bravo

AF:

0.000691

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000557

AC:

ExAC

AF:

0.000337

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.49

CADD

Benign

7.6

DANN

Benign

0.96

DEOGEN2

Benign

0.084

T;T;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.51

.;T;T

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.0064

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

N;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.090

N;N;N

REVEL

Benign

0.043

Sift

Benign

0.12

T;T;T

Sift4G

Benign

0.14

T;T;T

Polyphen

0.20

B;B;.

Vest4

0.29

MutPred

0.31

Gain of catalytic residue at G329 (P = 0.002);Gain of catalytic residue at G329 (P = 0.002);Gain of catalytic residue at G329 (P = 0.002);

MVP

0.15

MPC

1.1

ClinPred

0.020

GERP RS

-2.8

Varity_R

0.068

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