dbSNP rs3227: ITPR3:c.7786-406G>A (chr6-33694518-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002224.4(ITPR3):c.7786-406G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000541 in 251,202 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

ITPR3
NM_002224.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.294

Publications

19 publications found

Variant links:

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 links:

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)

UQCC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BS2

High AC in GnomAd4 at 131 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR3	NM_002224.4 link	c.7786-406G>A		intron_variant	Intron 56 of 57	ENST00000605930.3	NP_002215.2	Q14573A6H8K3Q59ES2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ITPR3	ENST00000605930.3 link	c.7786-406G>A	intron_variant	Intron 56 of 57	1	NM_002224.4	ENSP00000475177.1	Q14573
UQCC2	ENST00000606961.1 link	n.4140C>T	non_coding_transcript_exon_variant	Exon 1 of 1	6
ITPR3	ENST00000374316.9 link	c.7786-406G>A	intron_variant	Intron 57 of 58	5		ENSP00000363435.4	Q14573

Frequencies

GnomAD3 genomes

AF:

0.000868

AC:

132

AN:

152004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00300

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000958

GnomAD4 exome

AF:

0.0000505

AC:

AN:

99080

Hom.:

Cov.:

AF XY:

0.0000373

AC XY:

AN XY:

53634

show subpopulations

African (AFR)

AF:

0.00284

AC:

AN:

1058

American (AMR)

AF:

0.00

AC:

AN:

2180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2240

East Asian (EAS)

AF:

0.00

AC:

AN:

1246

South Asian (SAS)

AF:

0.0000500

AC:

AN:

20018

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6184

Middle Eastern (MID)

AF:

0.00234

AC:

AN:

428

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

60466

Other (OTH)

AF:

0.00

AC:

AN:

5260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.615

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000861

AC:

131

AN:

152122

Hom.:

Cov.:

AF XY:

0.000726

AC XY:

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.00296

AC:

123

AN:

41516

American (AMR)

AF:

0.000392

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5140

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67972

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

832

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.2

(source)

DANN

Benign

0.67

PhyloP100

0.29

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over