NM_002224.4:c.161-5381A>T

Variant names:

• chr6-33650385-A-T
• rs9394159
• NM_002224.4:c.161-5381A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002224.4(ITPR3):​c.161-5381A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 152,160 control chromosomes in the GnomAD database, including 15,944 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (15944 hom., cov: 33)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• Publications: 17 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPR3	NM_002224.4	MANE Select	c.161-5381A>T		intron	N/A	NP_002215.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPR3	ENST00000605930.3	TSL:1 MANE Select	c.161-5381A>T		intron	N/A	ENSP00000475177.1
	ITPR3	ENST00000374316.9	TSL:5	c.161-5381A>T		intron	N/A	ENSP00000363435.4

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69564 AN: 152042 Hom.: 15930 Cov.: 33

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.457 AC: 69605 AN: 152160 Hom.: 15944 Cov.: 33 AF XY: 0.459 AC XY: 34170 AN XY: 74382

African (AFR) AF: 0.419 AC: 17407 AN: 41510

American (AMR) AF: 0.426 AC: 6511 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1721 AN: 3470

East Asian (EAS) AF: 0.528 AC: 2739 AN: 5184

South Asian (SAS) AF: 0.523 AC: 2520 AN: 4820

European-Finnish (FIN) AF: 0.463 AC: 4899 AN: 10588

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32200 AN: 67980

Other (OTH) AF: 0.492 AC: 1039 AN: 2110

Alfa AF: 0.475 Hom.: 9513

Bravo AF: 0.451

Asia WGS AF: 0.551 AC: 1916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.79
PhyloP100		-0.0070
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: rs9394159; hg19: chr6-33618162;