Variant chr6-33694890-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.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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.05

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPR3	NM_002224.4 linkuse as main transcript	c.7786-34C>T		intron_variant		ENST00000605930.3

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
ITPR3	ENST00000605930.3 linkuse as main transcript	c.7786-34C>T	intron_variant		1	NM_002224.4	P1
ITPR3	ENST00000374316.9 linkuse as main transcript	c.7786-34C>T	intron_variant		5		P1
UQCC2	ENST00000606961.1 linkuse as main transcript	n.3768G>A	non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21108

AN:

152092

Hom.:

1592

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.112

AC:

28090

AN:

250712

Hom.:

1868

AF XY:

0.112

AC XY:

15126

AN XY:

135638

show subpopulations

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 SAS exome

AF:

0.0602

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.:

AF XY:

0.133

AC XY:

96839

AN XY:

726974

show subpopulations

Gnomad4 AFR exome

AF:

0.164

Gnomad4 AMR exome

AF:

0.0828

Gnomad4 ASJ exome

AF:

0.0919

Gnomad4 EAS exome

AF:

0.0352

Gnomad4 SAS exome

AF:

0.0589

Gnomad4 FIN exome

AF:

0.109

Gnomad4 NFE exome

AF:

0.149

Gnomad4 OTH exome

AF:

0.126

GnomAD4 genome

AF:

0.139

AC:

21132

AN:

152210

Hom.:

1597

Cov.:

AF XY:

0.136

AC XY:

10100

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.165

Gnomad4 AMR

AF:

0.105

Gnomad4 ASJ

AF:

0.0891

Gnomad4 EAS

AF:

0.0251

Gnomad4 SAS

AF:

0.0529

Gnomad4 FIN

AF:

0.108

Gnomad4 NFE

AF:

0.152

Gnomad4 OTH

AF:

0.145

Alfa

AF:

0.142

Hom.:

3308

Bravo

AF:

0.141

Asia WGS

AF:

0.0570

AC:

200

AN:

3478

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

-0.79

CADD

Benign

1.2

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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