6-33655890-A-ATG

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_002224.4(ITPR3):c.282+14_282+15dup variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,613,244 control chromosomes in the GnomAD database, including 19 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0040 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (14 hom.)
• Consequence: ITPR3 NM_002224.4 splice_donor_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.480

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 6-33655890-A-ATG is Benign according to our data. Variant chr6-33655890-A-ATG is described in ClinVar as [Benign]. Clinvar id is 1170819.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 582 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPR3	NM_002224.4	c.282+14_282+15dup		splice_donor_region_variant, intron_variant		ENST00000605930.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPR3	ENST00000605930.3	c.282+14_282+15dup		splice_donor_region_variant, intron_variant		1	NM_002224.4	P1
ITPR3	ENST00000374316.9	c.282+14_282+15dup		splice_donor_region_variant, intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.00383 AC: 582 AN: 152078 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00925

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00163

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00243 AC: 607 AN: 249674 Hom.: 5 AF XY: 0.00244 AC XY: 330 AN XY: 135066

Gnomad AFR exome AF: 0.00968

Gnomad AMR exome AF: 0.00296

Gnomad ASJ exome AF: 0.00130

Gnomad EAS exome AF: 0.000708

Gnomad SAS exome AF: 0.00378

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.00163

Gnomad OTH exome AF: 0.00377

GnomAD4 exome AF: 0.00163 AC: 2382 AN: 1461048 Hom.: 14 Cov.: 31 AF XY: 0.00167 AC XY: 1211 AN XY: 726840

Gnomad4 AFR exome AF: 0.00855

Gnomad4 AMR exome AF: 0.00300

Gnomad4 ASJ exome AF: 0.00103

Gnomad4 EAS exome AF: 0.000378

Gnomad4 SAS exome AF: 0.00383

Gnomad4 FIN exome AF: 0.0000563

Gnomad4 NFE exome AF: 0.00120

Gnomad4 OTH exome AF: 0.00283

GnomAD4 genome AF: 0.00396 AC: 603 AN: 152196 Hom.: 5 Cov.: 32 AF XY: 0.00414 AC XY: 308 AN XY: 74422

Gnomad4 AFR AF: 0.00975

Gnomad4 AMR AF: 0.00320

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.00353

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00163

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00327 Hom.: 1

Bravo AF: 0.00440

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.00257

EpiControl AF: 0.00303

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 10, 2022

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs149835704; hg19: chr6-33623667;