6-33694518-G-C

Variant names:

• chr6-33694518-G-C
• rs3227
• NM_002224.4:c.7786-406G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002224.4(ITPR3):​c.7786-406G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 250,844 control chromosomes in the GnomAD database, including 30,604 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 0.42 (15673 hom., cov: 32)
  • Exomes 𝑓: 0.54 (14931 hom.)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294

Genes affected

ITPR3 (HGNC:6182): (inositol 1,4,5-trisphosphate receptor type 3) This gene encodes a receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium. The receptor contains a calcium channel at the C-terminus and the ligand-binding site at the N-terminus. Knockout studies in mice suggest that type 2 and type 3 inositol 1,4,5-trisphosphate receptors play a key role in exocrine secretion underlying energy metabolism and growth. [provided by RefSeq, Aug 2010]

UQCC2 (HGNC:21237): (ubiquinol-cytochrome c reductase complex assembly factor 2) This gene encodes a nucleoid protein localized to the mitochondria inner membrane. The encoded protein affects regulation of insulin secretion, mitochondrial ATP production, and myogenesis through modulation of mitochondrial respiratory chain activity. [provided by RefSeq, Oct 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR3	NM_002224.4	c.7786-406G>C		intron_variant	Intron 56 of 57	ENST00000605930.3	NP_002215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR3	ENST00000605930.3	c.7786-406G>C		intron_variant	Intron 56 of 57	1	NM_002224.4	ENSP00000475177.1
ITPR3	ENST00000374316.9	c.7786-406G>C		intron_variant	Intron 57 of 58	5		ENSP00000363435.4
UQCC2	ENST00000606961.1	n.4140C>G		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63413 AN: 151966 Hom.: 15675 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.397

GnomAD4 exome AF: 0.536 AC: 52900 AN: 98760 Hom.: 14931 Cov.: 0 AF XY: 0.563 AC XY: 30075 AN XY: 53458

Gnomad4 AFR exome AF: 0.177

Gnomad4 AMR exome AF: 0.576

Gnomad4 ASJ exome AF: 0.484

Gnomad4 EAS exome AF: 0.844

Gnomad4 SAS exome AF: 0.739

Gnomad4 FIN exome AF: 0.579

Gnomad4 NFE exome AF: 0.468

Gnomad4 OTH exome AF: 0.496

GnomAD4 genome AF: 0.417 AC: 63424 AN: 152084 Hom.: 15673 Cov.: 32 AF XY: 0.437 AC XY: 32460 AN XY: 74342

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.864

Gnomad4 SAS AF: 0.761

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.400

Alfa AF: 0.291 Hom.: 832

Bravo AF: 0.396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.9
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs3227; hg19: chr6-33662295;