6-33668455-T-C

Variant names:

• chr6-33668455-T-C
• rs9380372
• NM_002224.4:c.1887-60T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002224.4(ITPR3):​c.1887-60T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 1,607,482 control chromosomes in the GnomAD database, including 566,742 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (51071 hom., cov: 30)
  • Exomes 𝑓: 0.84 (515671 hom.)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.860
• Publications: 4 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-33668455-T-C is Benign according to our data. Variant chr6-33668455-T-C is described in ClinVar as Benign. ClinVar VariationId is 1237321.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR3	NM_002224.4	c.1887-60T>C		intron_variant	Intron 16 of 57	ENST00000605930.3	NP_002215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR3	ENST00000605930.3	c.1887-60T>C		intron_variant	Intron 16 of 57	1	NM_002224.4	ENSP00000475177.1
ITPR3	ENST00000374316.9	c.1887-60T>C		intron_variant	Intron 17 of 58	5		ENSP00000363435.4

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124315 AN: 151884 Hom.: 51024 Cov.: 30

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.936

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.805

GnomAD4 exome AF: 0.841 AC: 1224207 AN: 1455478 Hom.: 515671 AF XY: 0.845 AC XY: 610949 AN XY: 723364

African (AFR) AF: 0.762 AC: 25446 AN: 33402

American (AMR) AF: 0.825 AC: 36609 AN: 44388

Ashkenazi Jewish (ASJ) AF: 0.846 AC: 21618 AN: 25566

East Asian (EAS) AF: 0.850 AC: 33672 AN: 39598

South Asian (SAS) AF: 0.934 AC: 79771 AN: 85440

European-Finnish (FIN) AF: 0.869 AC: 46140 AN: 53094

Middle Eastern (MID) AF: 0.825 AC: 4736 AN: 5742

European-Non Finnish (NFE) AF: 0.836 AC: 926069 AN: 1108154

Other (OTH) AF: 0.834 AC: 50146 AN: 60094

GnomAD4 genome AF: 0.819 AC: 124419 AN: 152004 Hom.: 51071 Cov.: 30 AF XY: 0.822 AC XY: 61108 AN XY: 74304

African (AFR) AF: 0.762 AC: 31580 AN: 41432

American (AMR) AF: 0.813 AC: 12424 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2926 AN: 3466

East Asian (EAS) AF: 0.842 AC: 4325 AN: 5138

South Asian (SAS) AF: 0.937 AC: 4519 AN: 4822

European-Finnish (FIN) AF: 0.881 AC: 9335 AN: 10594

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.834 AC: 56650 AN: 67946

Other (OTH) AF: 0.807 AC: 1707 AN: 2114

Alfa AF: 0.814 Hom.: 7200

Bravo AF: 0.808

Asia WGS AF: 0.896 AC: 3117 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.35
DANN	Benign	0.28
PhyloP100		-0.86
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: rs9380372; hg19: chr6-33636232;