rs12205634

Variant names:

• chr6-33643890-C-G
• rs12205634
• NM_002224.4:c.160+3336C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-33643890-C-G
• chr6-33643890-C-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.160+3336C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,146 control chromosomes in the GnomAD database, including 3,119 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 0.18 (3119 hom., cov: 32)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.245 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.160+3336C>G		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.160+3336C>G		intron	N/A	ENSP00000475177.1	Q14573
	ITPR3	ENST00000374316.9	TSL:5	c.160+3336C>G		intron	N/A	ENSP00000363435.4	Q14573
	ITPR3	ENST00000931640.1		c.160+3336C>G		intron	N/A	ENSP00000601699.1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27155 AN: 152028 Hom.: 3121 Cov.: 32

Gnomad AFR AF: 0.0379

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.178 AC: 27153 AN: 152146 Hom.: 3119 Cov.: 32 AF XY: 0.186 AC XY: 13825 AN XY: 74372

African (AFR) AF: 0.0378 AC: 1571 AN: 41530

American (AMR) AF: 0.228 AC: 3483 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 979 AN: 3470

East Asian (EAS) AF: 0.148 AC: 764 AN: 5178

South Asian (SAS) AF: 0.257 AC: 1237 AN: 4822

European-Finnish (FIN) AF: 0.314 AC: 3311 AN: 10560

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.224 AC: 15214 AN: 67982

Other (OTH) AF: 0.149 AC: 314 AN: 2110

Alfa AF: 0.132 Hom.: 285

Bravo AF: 0.164

Asia WGS AF: 0.154 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.41
DANN	Benign	0.67
PhyloP100		-1.9
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: rs12205634; hg19: chr6-33611667;