rs3818527

Variant names:

• chr6-33693258-G-A
• rs3818527
• NM_002224.4:c.7625-287G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-33693258-G-A
• chr6-33693258-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002224.4(ITPR3):​c.7625-287G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,940 control chromosomes in the GnomAD database, including 15,658 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 (15658 hom., cov: 32)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423
• Publications: 13 publications found

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]

UQCC2 Gene-Disease associations (from GenCC):

• mitochondrial complex III deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• mitochondrial complex III deficiency nuclear type 7

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002224.4. 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
	ITPR3	NM_002224.4	MANE Select	c.7625-287G>A		intron	N/A	NP_002215.2	Q14573

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPR3	ENST00000605930.3	TSL:1 MANE Select	c.7625-287G>A		intron	N/A	ENSP00000475177.1	Q14573
	ITPR3	ENST00000374316.9	TSL:5	c.7625-287G>A		intron	N/A	ENSP00000363435.4	Q14573
	ITPR3	ENST00000931640.1		c.7595-287G>A		intron	N/A	ENSP00000601699.1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63374 AN: 151822 Hom.: 15660 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.395

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.417 AC: 63385 AN: 151940 Hom.: 15658 Cov.: 32 AF XY: 0.437 AC XY: 32443 AN XY: 74280

African (AFR) AF: 0.180 AC: 7441 AN: 41404

American (AMR) AF: 0.517 AC: 7903 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1630 AN: 3468

East Asian (EAS) AF: 0.863 AC: 4446 AN: 5154

South Asian (SAS) AF: 0.761 AC: 3672 AN: 4824

European-Finnish (FIN) AF: 0.606 AC: 6399 AN: 10562

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30468 AN: 67942

Other (OTH) AF: 0.398 AC: 835 AN: 2098

Alfa AF: 0.368 Hom.: 6552

Bravo AF: 0.395

Asia WGS AF: 0.721 AC: 2508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.9
DANN	Benign	0.87
PhyloP100		-0.42
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: rs3818527; hg19: chr6-33661035;