rs1324966

Variant names:

• chr6-33695674-C-T
• rs1324966
• NM_002224.4:c.7948-38C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-33695674-C-T
• chr6-33695674-C-A

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.7948-38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 1,597,064 control chromosomes in the GnomAD database, including 1,090 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.053 (356 hom., cov: 33)
  • Exomes 𝑓: 0.024 (734 hom.)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.886
• 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]

UQCC2 (HGNC:21237): (ubiquinol-cytochrome c reductase complex assembly factor 2) This gene encodes a nucleoid protein localized to the mitochondria inner membrane. The encoded protein affects regulation of insulin secretion, mitochondrial ATP production, and myogenesis through modulation of mitochondrial respiratory chain activity. [provided by RefSeq, Oct 2012]

UQCC2 Gene-Disease associations (from GenCC):

• mitochondrial complex III deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• mitochondrial complex III deficiency nuclear type 7

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-33695674-C-T is Benign according to our data. Variant chr6-33695674-C-T is described in ClinVar as Benign. ClinVar VariationId is 1293143.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 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.7948-38C>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.7948-38C>T		intron	N/A	ENSP00000475177.1	Q14573
	UQCC2	ENST00000887985.1		c.*879G>A		3_prime_UTR	Exon 5 of 5	ENSP00000558044.1
	UQCC2	ENST00000966149.1		c.*872G>A		3_prime_UTR	Exon 5 of 5	ENSP00000636208.1

Frequencies

GnomAD3 genomes AF: 0.0529 AC: 8055 AN: 152224 Hom.: 351 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0361

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.0402

Gnomad SAS AF: 0.0488

Gnomad FIN AF: 0.0197

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0559

GnomAD2 exomes AF: 0.0328 AC: 8207 AN: 250288 AF XY: 0.0324

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.0224

Gnomad ASJ exome AF: 0.0147

Gnomad EAS exome AF: 0.0408

Gnomad FIN exome AF: 0.0197

Gnomad NFE exome AF: 0.0225

Gnomad OTH exome AF: 0.0323

GnomAD4 exome AF: 0.0245 AC: 35345 AN: 1444722 Hom.: 734 Cov.: 28 AF XY: 0.0253 AC XY: 18168 AN XY: 719370

African (AFR) AF: 0.126 AC: 4168 AN: 33144

American (AMR) AF: 0.0245 AC: 1092 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.0155 AC: 403 AN: 26012

East Asian (EAS) AF: 0.0382 AC: 1513 AN: 39570

South Asian (SAS) AF: 0.0481 AC: 4133 AN: 85916

European-Finnish (FIN) AF: 0.0211 AC: 1118 AN: 53012

Middle Eastern (MID) AF: 0.0424 AC: 243 AN: 5736

European-Non Finnish (NFE) AF: 0.0188 AC: 20664 AN: 1096896

Other (OTH) AF: 0.0336 AC: 2011 AN: 59806

GnomAD4 genome AF: 0.0531 AC: 8091 AN: 152342 Hom.: 356 Cov.: 33 AF XY: 0.0530 AC XY: 3952 AN XY: 74498

African (AFR) AF: 0.125 AC: 5206 AN: 41566

American (AMR) AF: 0.0361 AC: 552 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3472

East Asian (EAS) AF: 0.0403 AC: 209 AN: 5190

South Asian (SAS) AF: 0.0493 AC: 238 AN: 4830

European-Finnish (FIN) AF: 0.0197 AC: 209 AN: 10630

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0219 AC: 1490 AN: 68028

Other (OTH) AF: 0.0587 AC: 124 AN: 2114

Alfa AF: 0.0419 Hom.: 51

Bravo AF: 0.0568

Asia WGS AF: 0.0680 AC: 236 AN: 3478

EpiCase AF: 0.0212

EpiControl AF: 0.0239

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.68
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1324966; hg19: chr6-33663451;