6-33656527-TC-T

Variant names:

• chr6-33656527-TC-T
• rs5875456
• NM_002224.4:c.282+642delC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_002224.4(ITPR3):​c.282+642delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,106 control chromosomes in the GnomAD database, including 3,768 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3768 hom., cov: 27)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110
• Publications: 0 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]

ITPR3 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease, demyelinating, type 1J

  Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR3	NM_002224.4	c.282+642delC		intron_variant	Intron 3 of 57	ENST00000605930.3	NP_002215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR3	ENST00000605930.3	c.282+641delC		intron_variant	Intron 3 of 57	1	NM_002224.4	ENSP00000475177.1
ITPR3	ENST00000374316.9	c.282+641delC		intron_variant	Intron 4 of 58	5		ENSP00000363435.4

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30911 AN: 151986 Hom.: 3769 Cov.: 27

Gnomad AFR AF: 0.0675

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.203 AC: 30914 AN: 152106 Hom.: 3768 Cov.: 27 AF XY: 0.211 AC XY: 15716 AN XY: 74330

African (AFR) AF: 0.0674 AC: 2801 AN: 41530

American (AMR) AF: 0.255 AC: 3894 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 984 AN: 3468

East Asian (EAS) AF: 0.280 AC: 1442 AN: 5148

South Asian (SAS) AF: 0.294 AC: 1416 AN: 4820

European-Finnish (FIN) AF: 0.351 AC: 3718 AN: 10590

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16013 AN: 67954

Other (OTH) AF: 0.173 AC: 365 AN: 2110

Alfa AF: 0.231 Hom.: 576

Bravo AF: 0.189

Asia WGS AF: 0.219 AC: 765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.11
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: rs5875456; hg19: chr6-33624304;