chr6-116792598-A-AGG

Variant names:

• chr6-116792598-A-AGG
• rs550458778
• NM_148963.4:c.2324_2325insCC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_148963.4(GPRC6A):​c.2324_2325insCC​(p.Glu776LeufsTer19) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0892 in 1,612,338 control chromosomes in the GnomAD database, including 10,385 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (3332 hom., cov: 33)
  • Exomes 𝑓: 0.081 (7053 hom.)
• Consequence: GPRC6A NM_148963.4 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.75

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 6-116792598-A-AGG is Benign according to our data. Variant chr6-116792598-A-AGG is described in ClinVar as [Benign]. Clinvar id is 769689.Status of the report is criteria_provided_single_submitter, 1 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 rank	MANE	Protein	UniProt
GPRC6A	NM_148963.4	c.2324_2325insCC	p.Glu776LeufsTer19	frameshift_variant	Exon 6 of 6	ENST00000310357.8	NP_683766.2
GPRC6A	NM_001286355.1	c.2111_2112insCC	p.Glu705LeufsTer19	frameshift_variant	Exon 5 of 5		NP_001273284.1
GPRC6A	NM_001286354.1	c.1799_1800insCC	p.Glu601LeufsTer19	frameshift_variant	Exon 6 of 6		NP_001273283.1
GPRC6A	XM_017010475.2	c.2183_2184insCC	p.Glu729LeufsTer19	frameshift_variant	Exon 7 of 7		XP_016865964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPRC6A	ENST00000310357.8	c.2324_2325insCC	p.Glu776LeufsTer19	frameshift_variant	Exon 6 of 6	1	NM_148963.4	ENSP00000309493.4
GPRC6A	ENST00000368549.7	c.2111_2112insCC	p.Glu705LeufsTer19	frameshift_variant	Exon 5 of 5	1		ENSP00000357537.3
GPRC6A	ENST00000530250.1	c.1799_1800insCC	p.Glu601LeufsTer19	frameshift_variant	Exon 6 of 6	1		ENSP00000433465.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24977 AN: 152008 Hom.: 3321 Cov.: 33

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

GnomAD2 exomes AF: 0.0493 AC: 10989 AN: 222804 AF XY: 0.0439

Gnomad AFR exome AF: 0.233

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.0448

Gnomad EAS exome AF: 0.00214

Gnomad FIN exome AF: 0.0574

Gnomad NFE exome AF: 0.0287

Gnomad OTH exome AF: 0.0387

GnomAD4 exome AF: 0.0814 AC: 118818 AN: 1460212 Hom.: 7053 Cov.: 37 AF XY: 0.0791 AC XY: 57457 AN XY: 726188

Gnomad4 AFR exome AF: 0.374 AC: 12499 AN: 33422

Gnomad4 AMR exome AF: 0.207 AC: 9205 AN: 44576

Gnomad4 ASJ exome AF: 0.105 AC: 2741 AN: 26104

Gnomad4 EAS exome AF: 0.0134 AC: 530 AN: 39672

Gnomad4 SAS exome AF: 0.0608 AC: 5238 AN: 86096

Gnomad4 FIN exome AF: 0.110 AC: 5871 AN: 53266

Gnomad4 NFE exome AF: 0.0690 AC: 76660 AN: 1110982

Gnomad4 Remaining exome AF: 0.0912 AC: 5505 AN: 60334

GnomAD4 genome AF: 0.165 AC: 25032 AN: 152126 Hom.: 3332 Cov.: 33 AF XY: 0.164 AC XY: 12202 AN XY: 74396

Gnomad4 AFR AF: 0.373 AC: 0.373166 AN: 0.373166

Gnomad4 AMR AF: 0.163 AC: 0.162651 AN: 0.162651

Gnomad4 ASJ AF: 0.106 AC: 0.105825 AN: 0.105825

Gnomad4 EAS AF: 0.00907 AC: 0.00906986 AN: 0.00906986

Gnomad4 SAS AF: 0.0652 AC: 0.0652444 AN: 0.0652444

Gnomad4 FIN AF: 0.115 AC: 0.114978 AN: 0.114978

Gnomad4 NFE AF: 0.0694 AC: 0.0693787 AN: 0.0693787

Gnomad4 OTH AF: 0.148 AC: 0.148201 AN: 0.148201

Alfa AF: 0.0266 Hom.: 38

Asia WGS AF: 0.0570 AC: 201 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mutation Taster		=141/59	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs550458778; hg19: chr6-117113761; COSMIC: COSV59953072;