chr6-116792599-T-TA

Position:

• chr6-116792599-T-TA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_148963.4(GPRC6A):​c.2323_2324insT​(p.Tyr775LeufsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0892 in 1,612,340 control chromosomes in the GnomAD database, including 10,382 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (3331 hom., cov: 30)
  • Exomes 𝑓: 0.081 (7051 hom.)
• Consequence: GPRC6A NM_148963.4 frameshift
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00500

Genes affected

GPRC6A (HGNC:18510): (G protein-coupled receptor class C group 6 member A) Members of family C of the G protein-coupled receptor (GPCR) superfamily, such as GPRC6A, are characterized by an evolutionarily conserved amino acid-sensing motif linked to an intramembranous 7-transmembrane loop region. Several members of GPCR family C, including GPRC6A, also have a long N-terminal domain (summary by Pi et al., 2005 [PubMed 16199532]).[supplied by OMIM, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 6-116792599-T-TA is Benign according to our data. Variant chr6-116792599-T-TA is described in ClinVar as [Benign]. Clinvar id is 769690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPRC6A	NM_148963.4	c.2323_2324insT	p.Tyr775LeufsTer2	frameshift_variant	6/6	ENST00000310357.8	NP_683766.2
GPRC6A	NM_001286354.1	c.1798_1799insT	p.Tyr600LeufsTer2	frameshift_variant	6/6		NP_001273283.1
GPRC6A	NM_001286355.1	c.2110_2111insT	p.Tyr704LeufsTer2	frameshift_variant	5/5		NP_001273284.1
GPRC6A	XM_017010475.2	c.2182_2183insT	p.Tyr728LeufsTer2	frameshift_variant	7/7		XP_016865964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPRC6A	ENST00000310357.8	c.2323_2324insT	p.Tyr775LeufsTer2	frameshift_variant	6/6	1	NM_148963.4	ENSP00000309493	P1
GPRC6A	ENST00000368549.7	c.2110_2111insT	p.Tyr704LeufsTer2	frameshift_variant	5/5	1		ENSP00000357537
GPRC6A	ENST00000530250.1	c.1798_1799insT	p.Tyr600LeufsTer2	frameshift_variant	6/6	1		ENSP00000433465

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24977 AN: 152002 Hom.: 3320 Cov.: 30

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.00905

Gnomad SAS AF: 0.0652

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0694

Gnomad OTH AF: 0.150

GnomAD3 exomes AF: 0.0440 AC: 9812 AN: 223232 Hom.: 1393 AF XY: 0.0390 AC XY: 4757 AN XY: 121942

Gnomad AFR exome AF: 0.208

Gnomad AMR exome AF: 0.0944

Gnomad ASJ exome AF: 0.0384

Gnomad EAS exome AF: 0.00170

Gnomad SAS exome AF: 0.0199

Gnomad FIN exome AF: 0.0526

Gnomad NFE exome AF: 0.0256

Gnomad OTH exome AF: 0.0347

GnomAD4 exome AF: 0.0814 AC: 118847 AN: 1460220 Hom.: 7051 Cov.: 36 AF XY: 0.0791 AC XY: 57472 AN XY: 726186

Gnomad4 AFR exome AF: 0.374

Gnomad4 AMR exome AF: 0.207

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.0134

Gnomad4 SAS exome AF: 0.0608

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.0690

Gnomad4 OTH exome AF: 0.0913

GnomAD4 genome AF: 0.165 AC: 25032 AN: 152120 Hom.: 3331 Cov.: 30 AF XY: 0.164 AC XY: 12202 AN XY: 74394

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.00907

Gnomad4 SAS AF: 0.0652

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.0694

Gnomad4 OTH AF: 0.148

Alfa AF: 0.0413 Hom.: 35

Asia WGS AF: 0.0570 AC: 201 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 18, 2020	This variant is associated with the following publications: (PMID: 31373687) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

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: rs371464745; hg19: chr6-117113762;