6-116792598-A-AGGT

Variant names:

• chr6-116792598-A-AGGT
• rs550458778
• NM_148963.4:c.2324_2325insACC

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_148963.4(GPRC6A):​c.2324_2325insACC​(p.Tyr775delinsTerPro) variant causes a stop gained, disruptive inframe insertion change involving the alteration of a conserved nucleotide. 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: 33)
• Consequence: GPRC6A NM_148963.4 stop_gained, disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.75
• Publications: 5 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: Uncertain_significance. The variant received 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.

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.2324_2325insACC	p.Tyr775delinsTerPro	stop_gained disruptive_inframe_insertion	Exon 6 of 6	NP_683766.2	Q5T6X5-1
	GPRC6A	NM_001286355.1		c.2111_2112insACC	p.Tyr704delinsTerPro	stop_gained disruptive_inframe_insertion	Exon 5 of 5	NP_001273284.1	Q5T6X5-3
	GPRC6A	NM_001286354.1		c.1799_1800insACC	p.Tyr600delinsTerPro	stop_gained disruptive_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.2324_2325insACC	p.Tyr775delinsTerPro	stop_gained disruptive_inframe_insertion	Exon 6 of 6	ENSP00000309493.4	Q5T6X5-1
	GPRC6A	ENST00000368549.7	TSL:1	c.2111_2112insACC	p.Tyr704delinsTerPro	stop_gained disruptive_inframe_insertion	Exon 5 of 5	ENSP00000357537.3	Q5T6X5-3
	GPRC6A	ENST00000530250.1	TSL:1	c.1799_1800insACC	p.Tyr600delinsTerPro	stop_gained disruptive_inframe_insertion	Exon 6 of 6	ENSP00000433465.1	Q5T6X5-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 38

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.8
Mutation Taster		=87/113	disease causing

Splicing

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

Other links and lift over

dbSNP: rs550458778; hg19: chr6-117113761; COSMIC: COSV106059759;