chr14-91234208-G-C

Position:

• chr14-91234208-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001177676.2(GPR68):​c.843C>G​(p.Ala281=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00727 in 1,560,188 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0048 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0075 (45 hom.)
• Consequence: GPR68 NM_001177676.2 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.368

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 14-91234208-G-C is Benign according to our data. Variant chr14-91234208-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3055827.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.368 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR68	NM_001177676.2	c.843C>G	p.Ala281=	synonymous_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.843C>G	p.Ala281=	synonymous_variant	2/2		NM_001177676.2	ENSP00000498702	P1
GPR68	ENST00000531499.2	c.843C>G	p.Ala281=	synonymous_variant	2/2	1		ENSP00000434045	P1
GPR68	ENST00000535815.5	c.843C>G	p.Ala281=	synonymous_variant	2/2	1		ENSP00000440797	P1
GPR68	ENST00000529102.1	c.843C>G	p.Ala281=	synonymous_variant	2/2	1		ENSP00000432740

Frequencies

GnomAD3 genomes AF: 0.00480 AC: 731 AN: 152252 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00726

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00732

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.00522 AC: 900 AN: 172454 Hom.: 5 AF XY: 0.00487 AC XY: 454 AN XY: 93190

Gnomad AFR exome AF: 0.000883

Gnomad AMR exome AF: 0.00674

Gnomad ASJ exome AF: 0.00296

Gnomad EAS exome AF: 0.0000751

Gnomad SAS exome AF: 0.000573

Gnomad FIN exome AF: 0.00153

Gnomad NFE exome AF: 0.00808

Gnomad OTH exome AF: 0.00940

GnomAD4 exome AF: 0.00754 AC: 10610 AN: 1407818 Hom.: 45 Cov.: 33 AF XY: 0.00718 AC XY: 5002 AN XY: 696782

Gnomad4 AFR exome AF: 0.00133

Gnomad4 AMR exome AF: 0.00709

Gnomad4 ASJ exome AF: 0.00260

Gnomad4 EAS exome AF: 0.0000538

Gnomad4 SAS exome AF: 0.000792

Gnomad4 FIN exome AF: 0.00137

Gnomad4 NFE exome AF: 0.00885

Gnomad4 OTH exome AF: 0.00733

GnomAD4 genome AF: 0.00478 AC: 729 AN: 152370 Hom.: 3 Cov.: 32 AF XY: 0.00435 AC XY: 324 AN XY: 74516

Gnomad4 AFR AF: 0.00149

Gnomad4 AMR AF: 0.00725

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00217

Gnomad4 NFE AF: 0.00730

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00260 Hom.: 0

Bravo AF: 0.00547

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

GPR68-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 21, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.3
DANN	Benign	0.70

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

Other links and lift over

dbSNP: rs150575263; hg19: chr14-91700552;