6-33624007-C-T

Variant names:

• chr6-33624007-C-T
• rs10947415
• NM_002224.4:c.89+2316C>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.89+2316C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,260 control chromosomes in the GnomAD database, including 1,797 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 0.13 (1797 hom., cov: 32)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.49
• Publications: 3 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPR3	NM_002224.4	MANE Select	c.89+2316C>T		intron	N/A	NP_002215.2	Q14573

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPR3	ENST00000605930.3	TSL:1 MANE Select	c.89+2316C>T		intron	N/A	ENSP00000475177.1	Q14573
	ITPR3	ENST00000374316.9	TSL:5	c.89+2316C>T		intron	N/A	ENSP00000363435.4	Q14573
	ITPR3	ENST00000931640.1		c.89+2316C>T		intron	N/A	ENSP00000601699.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20157 AN: 152142 Hom.: 1796 Cov.: 32

Gnomad AFR AF: 0.0416

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.00750

Gnomad SAS AF: 0.0651

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.132 AC: 20162 AN: 152260 Hom.: 1797 Cov.: 32 AF XY: 0.127 AC XY: 9456 AN XY: 74452

African (AFR) AF: 0.0416 AC: 1727 AN: 41556

American (AMR) AF: 0.146 AC: 2231 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 778 AN: 3470

East Asian (EAS) AF: 0.00751 AC: 39 AN: 5190

South Asian (SAS) AF: 0.0649 AC: 313 AN: 4822

European-Finnish (FIN) AF: 0.141 AC: 1494 AN: 10600

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13051 AN: 68002

Other (OTH) AF: 0.153 AC: 324 AN: 2114

Alfa AF: 0.162 Hom.: 857

Bravo AF: 0.130

Asia WGS AF: 0.0460 AC: 161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.068
DANN	Benign	0.64
PhyloP100		-3.5
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: rs10947415; hg19: chr6-33591784;