NM_002224.4:c.7225+160G>A

Variant names:

• chr6-33691269-G-A
• rs4711336
• NM_002224.4:c.7225+160G>A

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.7225+160G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,986 control chromosomes in the GnomAD database, including 16,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.43 (16889 hom., cov: 32)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.367
• Publications: 25 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=-0.87).
• BP6: Variant 6-33691269-G-A is Benign according to our data. Variant chr6-33691269-G-A is described in ClinVar as Benign. ClinVar VariationId is 1238783.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 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.7225+160G>A		intron	N/A	NP_002215.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPR3	ENST00000605930.3	TSL:1 MANE Select	c.7225+160G>A		intron	N/A	ENSP00000475177.1
	UQCC2	ENST00000966148.1		c.*1597C>T		3_prime_UTR	Exon 5 of 5	ENSP00000636207.1
	ITPR3	ENST00000374316.9	TSL:5	c.7225+160G>A		intron	N/A	ENSP00000363435.4

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65935 AN: 151880 Hom.: 16879 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.434 AC: 65959 AN: 151986 Hom.: 16889 Cov.: 32 AF XY: 0.454 AC XY: 33715 AN XY: 74274

African (AFR) AF: 0.190 AC: 7873 AN: 41420

American (AMR) AF: 0.530 AC: 8105 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1673 AN: 3468

East Asian (EAS) AF: 0.900 AC: 4649 AN: 5168

South Asian (SAS) AF: 0.803 AC: 3859 AN: 4804

European-Finnish (FIN) AF: 0.625 AC: 6603 AN: 10564

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.467 AC: 31714 AN: 67970

Other (OTH) AF: 0.421 AC: 890 AN: 2112

Alfa AF: 0.455 Hom.: 28252

Bravo AF: 0.410

ClinVar

ClinVar submissions as Germline

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	-0.87
CADD	Benign	2.5
DANN	Benign	0.71
PhyloP100		-0.37
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: rs4711336; hg19: chr6-33659046;