rs111974433

Variant names:

• chr6-116792602-T-TTAC
• rs111974433
• NM_148963.4:c.2320_2321insGTA

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_148963.4(GPRC6A):​c.2320_2321insGTA​(p.Gly773_Lys774insSer) variant causes a conservative inframe insertion change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: GPRC6A NM_148963.4 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.95

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_148963.4. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPRC6A	NM_148963.4	c.2320_2321insGTA	p.Gly773_Lys774insSer	conservative_inframe_insertion	Exon 6 of 6	ENST00000310357.8	NP_683766.2
GPRC6A	NM_001286355.1	c.2107_2108insGTA	p.Gly702_Lys703insSer	conservative_inframe_insertion	Exon 5 of 5		NP_001273284.1
GPRC6A	NM_001286354.1	c.1795_1796insGTA	p.Gly598_Lys599insSer	conservative_inframe_insertion	Exon 6 of 6		NP_001273283.1
GPRC6A	XM_017010475.2	c.2179_2180insGTA	p.Gly726_Lys727insSer	conservative_inframe_insertion	Exon 7 of 7		XP_016865964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPRC6A	ENST00000310357.8	c.2320_2321insGTA	p.Gly773_Lys774insSer	conservative_inframe_insertion	Exon 6 of 6	1	NM_148963.4	ENSP00000309493.4
GPRC6A	ENST00000368549.7	c.2107_2108insGTA	p.Gly702_Lys703insSer	conservative_inframe_insertion	Exon 5 of 5	1		ENSP00000357537.3
GPRC6A	ENST00000530250.1	c.1795_1796insGTA	p.Gly598_Lys599insSer	conservative_inframe_insertion	Exon 6 of 6	1		ENSP00000433465.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs111974433; hg19: chr6-117113765;