6-33695278-G-A

Position:

• chr6-33695278-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000605930.3(ITPR3):​c.7947+193G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 632,062 control chromosomes in the GnomAD database, including 9,295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1881 hom., cov: 33)
  • Exomes 𝑓: 0.17 (7414 hom.)
• Consequence: ITPR3 ENST00000605930.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.873

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 6-33695278-G-A is Benign according to our data. Variant chr6-33695278-G-A is described in ClinVar as [Benign]. Clinvar id is 1238146.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR3	NM_002224.4	c.7947+193G>A		intron_variant		ENST00000605930.3	NP_002215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR3	ENST00000605930.3	c.7947+193G>A		intron_variant		1	NM_002224.4	ENSP00000475177	P1
ITPR3	ENST00000374316.9	c.7947+193G>A		intron_variant		5		ENSP00000363435	P1
UQCC2	ENST00000606961.1	n.3380C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20638 AN: 152174 Hom.: 1880 Cov.: 33

Gnomad AFR AF: 0.0363

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0459

Gnomad SAS AF: 0.0691

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.166 AC: 79517 AN: 479770 Hom.: 7414 Cov.: 6 AF XY: 0.162 AC XY: 40612 AN XY: 250414

Gnomad4 AFR exome AF: 0.0380

Gnomad4 AMR exome AF: 0.154

Gnomad4 ASJ exome AF: 0.226

Gnomad4 EAS exome AF: 0.0890

Gnomad4 SAS exome AF: 0.0758

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.163

GnomAD4 genome AF: 0.136 AC: 20643 AN: 152292 Hom.: 1881 Cov.: 33 AF XY: 0.130 AC XY: 9698 AN XY: 74460

Gnomad4 AFR AF: 0.0362

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.0458

Gnomad4 SAS AF: 0.0694

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.163

Alfa AF: 0.162 Hom.: 367

Bravo AF: 0.135

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	-0.85
CADD	Benign	0.73
DANN	Benign	0.28

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

Other links and lift over

dbSNP: rs2281918; hg19: chr6-33663055;