NM_002224.4:c.7786-34C>T

Variant names:

• chr6-33694890-C-T
• rs684119
• NM_002224.4:c.7786-34C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002224.4(ITPR3):​c.7786-34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,613,412 control chromosomes in the GnomAD database, including 15,992 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1597 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14395 hom.)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 6-33694890-C-T is Benign according to our data. Variant chr6-33694890-C-T is described in ClinVar as Benign. ClinVar VariationId is 1293591.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 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.7786-34C>T		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.7786-34C>T		intron	N/A	ENSP00000475177.1	Q14573
	UQCC2	ENST00000887985.1		c.*1663G>A		3_prime_UTR	Exon 5 of 5	ENSP00000558044.1
	UQCC2	ENST00000966149.1		c.*1656G>A		3_prime_UTR	Exon 5 of 5	ENSP00000636208.1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21108 AN: 152092 Hom.: 1592 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0891

Gnomad EAS AF: 0.0252

Gnomad SAS AF: 0.0534

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.147

GnomAD2 exomes AF: 0.112 AC: 28090 AN: 250712 AF XY: 0.112

Gnomad AFR exome AF: 0.163

Gnomad AMR exome AF: 0.0758

Gnomad ASJ exome AF: 0.0920

Gnomad EAS exome AF: 0.0216

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.146

Gnomad OTH exome AF: 0.121

GnomAD4 exome AF: 0.136 AC: 198223 AN: 1461202 Hom.: 14395 Cov.: 32 AF XY: 0.133 AC XY: 96839 AN XY: 726974

African (AFR) AF: 0.164 AC: 5496 AN: 33472

American (AMR) AF: 0.0828 AC: 3702 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0919 AC: 2401 AN: 26130

East Asian (EAS) AF: 0.0352 AC: 1396 AN: 39696

South Asian (SAS) AF: 0.0589 AC: 5078 AN: 86222

European-Finnish (FIN) AF: 0.109 AC: 5788 AN: 53184

Middle Eastern (MID) AF: 0.139 AC: 799 AN: 5766

European-Non Finnish (NFE) AF: 0.149 AC: 165944 AN: 1111646

Other (OTH) AF: 0.126 AC: 7619 AN: 60370

GnomAD4 genome AF: 0.139 AC: 21132 AN: 152210 Hom.: 1597 Cov.: 32 AF XY: 0.136 AC XY: 10100 AN XY: 74442

African (AFR) AF: 0.165 AC: 6846 AN: 41502

American (AMR) AF: 0.105 AC: 1609 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0891 AC: 309 AN: 3468

East Asian (EAS) AF: 0.0251 AC: 130 AN: 5186

South Asian (SAS) AF: 0.0529 AC: 255 AN: 4824

European-Finnish (FIN) AF: 0.108 AC: 1152 AN: 10618

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10301 AN: 67984

Other (OTH) AF: 0.145 AC: 307 AN: 2114

Alfa AF: 0.143 Hom.: 7149

Bravo AF: 0.141

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.2
DANN	Benign	0.81
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs684119; hg19: chr6-33662667; COSMIC: COSV65269193; COSMIC: COSV65269193;