6-116793060-T-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_148963.4(GPRC6A):​c.1863A>G​(p.Thr621Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,556 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GPRC6A NM_148963.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=-1.76 with no splicing effect.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461556 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 727080

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111802

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.0
DANN	Benign	0.63
PhyloP100		-1.8

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;