Variant chr6-33695674-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002224.4(ITPR3):c.7948-38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 1,597,064 control chromosomes in the GnomAD database, including 1,090 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.053 ( 356 hom., cov: 33)

Exomes 𝑓: 0.024 ( 734 hom. )

Consequence

ITPR3
NM_002224.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.886

Variant links:

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]

ITPR3 links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 6-33695674-C-T is Benign according to our data. Variant chr6-33695674-C-T is described in ClinVar as [Benign]. Clinvar id is 1293143.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR3	NM_002224.4 linkuse as main transcript	c.7948-38C>T		intron_variant		ENST00000605930.3	NP_002215.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
ITPR3	ENST00000605930.3 linkuse as main transcript	c.7948-38C>T	intron_variant		1	NM_002224.4	ENSP00000475177	P1
UQCC2	ENST00000374231.8 linkuse as main transcript	c.*31-226G>A	intron_variant		3		ENSP00000363348
ITPR3	ENST00000374316.9 linkuse as main transcript	c.7948-38C>T	intron_variant		5		ENSP00000363435	P1
UQCC2	ENST00000606961.1 linkuse as main transcript	n.2984G>A	non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0529

AC:

8055

AN:

152224

Hom.:

351

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0361

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.0402

Gnomad SAS

AF:

0.0488

Gnomad FIN

AF:

0.0197

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0219

Gnomad OTH

AF:

0.0559

GnomAD3 exomes

AF:

0.0328

AC:

8207

AN:

250288

Hom.:

223

AF XY:

0.0324

AC XY:

4386

AN XY:

135258

show subpopulations

Gnomad AFR exome

AF:

0.121

Gnomad AMR exome

AF:

0.0224

Gnomad ASJ exome

AF:

0.0147

Gnomad EAS exome

AF:

0.0408

Gnomad SAS exome

AF:

0.0460

Gnomad FIN exome

AF:

0.0197

Gnomad NFE exome

AF:

0.0225

Gnomad OTH exome

AF:

0.0323

GnomAD4 exome

AF:

0.0245

AC:

35345

AN:

1444722

Hom.:

734

Cov.:

AF XY:

0.0253

AC XY:

18168

AN XY:

719370

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.0245

Gnomad4 ASJ exome

AF:

0.0155

Gnomad4 EAS exome

AF:

0.0382

Gnomad4 SAS exome

AF:

0.0481

Gnomad4 FIN exome

AF:

0.0211

Gnomad4 NFE exome

AF:

0.0188

Gnomad4 OTH exome

AF:

0.0336

GnomAD4 genome

AF:

0.0531

AC:

8091

AN:

152342

Hom.:

356

Cov.:

AF XY:

0.0530

AC XY:

3952

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.125

Gnomad4 AMR

AF:

0.0361

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.0403

Gnomad4 SAS

AF:

0.0493

Gnomad4 FIN

AF:

0.0197

Gnomad4 NFE

AF:

0.0219

Gnomad4 OTH

AF:

0.0587

Alfa

AF:

0.0395

Hom.:

Bravo

AF:

0.0568

Asia WGS

AF:

0.0680

AC:

236

AN:

3478

EpiCase

AF:

0.0212

EpiControl

AF:

0.0239

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.5

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over