rs111974433

Variant names:

• chr6-116792602-T-TTCC
• rs111974433
• NM_148963.4:c.2320_2321insGGA

Your query was ambiguous. Multiple possible variants found:

• chr6-116792602-T-TTCC
• chr6-116792602-T-TTAC
• chr6-116792602-T-TTTCC

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 1P and 10B. PM4_Supporting BP6_Moderate BA1

The NM_148963.4(GPRC6A):​c.2320_2321insGGA​(p.Gly773_Lys774insArg) variant causes a conservative inframe insertion change. The variant allele was found at a frequency of 0.0892 in 1,612,534 control chromosomes in the GnomAD database, including 10,381 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (3331 hom., cov: 30)
  • Exomes 𝑓: 0.081 (7050 hom.)
• Consequence: GPRC6A NM_148963.4 conservative_inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.95
• Publications: 4 publications found

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 -9 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_148963.4. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 6-116792602-T-TTCC is Benign according to our data. Variant chr6-116792602-T-TTCC is described in ClinVar as Benign. ClinVar VariationId is 769691.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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_148963.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPRC6A	NM_148963.4	MANE Select	c.2320_2321insGGA	p.Gly773_Lys774insArg	conservative_inframe_insertion	Exon 6 of 6	NP_683766.2	Q5T6X5-1
	GPRC6A	NM_001286355.1		c.2107_2108insGGA	p.Gly702_Lys703insArg	conservative_inframe_insertion	Exon 5 of 5	NP_001273284.1	Q5T6X5-3
	GPRC6A	NM_001286354.1		c.1795_1796insGGA	p.Gly598_Lys599insArg	conservative_inframe_insertion	Exon 6 of 6	NP_001273283.1	Q5T6X5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPRC6A	ENST00000310357.8	TSL:1 MANE Select	c.2320_2321insGGA	p.Gly773_Lys774insArg	conservative_inframe_insertion	Exon 6 of 6	ENSP00000309493.4	Q5T6X5-1
	GPRC6A	ENST00000368549.7	TSL:1	c.2107_2108insGGA	p.Gly702_Lys703insArg	conservative_inframe_insertion	Exon 5 of 5	ENSP00000357537.3	Q5T6X5-3
	GPRC6A	ENST00000530250.1	TSL:1	c.1795_1796insGGA	p.Gly598_Lys599insArg	conservative_inframe_insertion	Exon 6 of 6	ENSP00000433465.1	Q5T6X5-2

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24977 AN: 151988 Hom.: 3320 Cov.: 30

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.00905

Gnomad SAS AF: 0.0651

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0694

Gnomad OTH AF: 0.150

GnomAD2 exomes AF: 0.0464 AC: 10048 AN: 216582 AF XY: 0.0409

Gnomad AFR exome AF: 0.247

Gnomad AMR exome AF: 0.106

Gnomad ASJ exome AF: 0.0407

Gnomad EAS exome AF: 0.00192

Gnomad FIN exome AF: 0.0516

Gnomad NFE exome AF: 0.0264

Gnomad OTH exome AF: 0.0368

GnomAD4 exome AF: 0.0814 AC: 118855 AN: 1460428 Hom.: 7050 Cov.: 36 AF XY: 0.0791 AC XY: 57471 AN XY: 726336

African (AFR) AF: 0.374 AC: 12503 AN: 33420

American (AMR) AF: 0.206 AC: 9202 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 2741 AN: 26108

East Asian (EAS) AF: 0.0134 AC: 530 AN: 39676

South Asian (SAS) AF: 0.0608 AC: 5239 AN: 86118

European-Finnish (FIN) AF: 0.110 AC: 5869 AN: 53274

Middle Eastern (MID) AF: 0.0988 AC: 569 AN: 5760

European-Non Finnish (NFE) AF: 0.0690 AC: 76695 AN: 1111154

Other (OTH) AF: 0.0913 AC: 5507 AN: 60334

GnomAD4 genome AF: 0.165 AC: 25032 AN: 152106 Hom.: 3331 Cov.: 30 AF XY: 0.164 AC XY: 12204 AN XY: 74372

African (AFR) AF: 0.373 AC: 15468 AN: 41446

American (AMR) AF: 0.162 AC: 2480 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 367 AN: 3466

East Asian (EAS) AF: 0.00907 AC: 47 AN: 5184

South Asian (SAS) AF: 0.0652 AC: 314 AN: 4818

European-Finnish (FIN) AF: 0.115 AC: 1219 AN: 10592

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0694 AC: 4720 AN: 68022

Other (OTH) AF: 0.148 AC: 313 AN: 2110

Alfa AF: 0.0211 Hom.: 35

Asia WGS AF: 0.0570 AC: 201 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.0
Mutation Taster		=76/24	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs111974433; hg19: chr6-117113765; COSMIC: COSV59951555;