chr6-116793060-T-A

Variant names:

• chr6-116793060-T-A
• rs6924002
• NM_148963.4:c.1863A>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_148963.4(GPRC6A):​c.1863A>T​(p.Thr621Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 1,613,426 control chromosomes in the GnomAD database, including 82,765 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.30 (7271 hom., cov: 33)
  • Exomes 𝑓: 0.32 (75494 hom.)
• Consequence: GPRC6A NM_148963.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• Publications: 16 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=-1.76 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPRC6A	NM_148963.4	c.1863A>T	p.Thr621Thr	synonymous_variant	Exon 6 of 6	ENST00000310357.8	NP_683766.2
GPRC6A	NM_001286355.1	c.1650A>T	p.Thr550Thr	synonymous_variant	Exon 5 of 5		NP_001273284.1
GPRC6A	NM_001286354.1	c.1338A>T	p.Thr446Thr	synonymous_variant	Exon 6 of 6		NP_001273283.1
GPRC6A	XM_017010475.2	c.1722A>T	p.Thr574Thr	synonymous_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.1863A>T	p.Thr621Thr	synonymous_variant	Exon 6 of 6	1	NM_148963.4	ENSP00000309493.4
GPRC6A	ENST00000368549.7	c.1650A>T	p.Thr550Thr	synonymous_variant	Exon 5 of 5	1		ENSP00000357537.3
GPRC6A	ENST00000530250.1	c.1338A>T	p.Thr446Thr	synonymous_variant	Exon 6 of 6	1		ENSP00000433465.1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45379 AN: 151986 Hom.: 7281 Cov.: 33

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.346

GnomAD2 exomes AF: 0.325 AC: 81565 AN: 250672 AF XY: 0.324

Gnomad AFR exome AF: 0.210

Gnomad AMR exome AF: 0.327

Gnomad ASJ exome AF: 0.478

Gnomad EAS exome AF: 0.547

Gnomad FIN exome AF: 0.259

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.337

GnomAD4 exome AF: 0.317 AC: 463011 AN: 1461322 Hom.: 75494 Cov.: 36 AF XY: 0.316 AC XY: 229967 AN XY: 726974

African (AFR) AF: 0.219 AC: 7340 AN: 33460

American (AMR) AF: 0.328 AC: 14646 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 12399 AN: 26124

East Asian (EAS) AF: 0.521 AC: 20673 AN: 39690

South Asian (SAS) AF: 0.261 AC: 22526 AN: 86224

European-Finnish (FIN) AF: 0.264 AC: 14119 AN: 53402

Middle Eastern (MID) AF: 0.433 AC: 2497 AN: 5762

European-Non Finnish (NFE) AF: 0.313 AC: 348172 AN: 1111600

Other (OTH) AF: 0.342 AC: 20639 AN: 60378

GnomAD4 genome AF: 0.298 AC: 45377 AN: 152104 Hom.: 7271 Cov.: 33 AF XY: 0.297 AC XY: 22085 AN XY: 74340

African (AFR) AF: 0.215 AC: 8904 AN: 41488

American (AMR) AF: 0.337 AC: 5148 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1661 AN: 3468

East Asian (EAS) AF: 0.527 AC: 2721 AN: 5160

South Asian (SAS) AF: 0.265 AC: 1280 AN: 4826

European-Finnish (FIN) AF: 0.257 AC: 2720 AN: 10584

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21656 AN: 67994

Other (OTH) AF: 0.345 AC: 729 AN: 2112

Alfa AF: 0.329 Hom.: 2824

Bravo AF: 0.305

Asia WGS AF: 0.371 AC: 1289 AN: 3478

EpiCase AF: 0.339

EpiControl AF: 0.330

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.79
DANN	Benign	0.62
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6924002; hg19: chr6-117114223; COSMIC: COSV59951600;