dbSNP rs764750465: ITPR3:p.Arg2671Ser (chr6-33695775-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002224.4(ITPR3):c.8011C>A(p.Arg2671Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,708 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: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ITPR3
NM_002224.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.80

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14914083).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR3	NM_002224.4 link	c.8011C>A	p.Arg2671Ser	missense_variant	Exon 58 of 58	ENST00000605930.3	NP_002215.2	Q14573A6H8K3Q59ES2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ITPR3	ENST00000605930.3 link	c.8011C>A	p.Arg2671Ser	missense_variant	Exon 58 of 58	1	NM_002224.4	ENSP00000475177.1	Q14573
ITPR3	ENST00000374316.9 link	c.8011C>A	p.Arg2671Ser	missense_variant	Exon 59 of 59	5		ENSP00000363435.4	Q14573
UQCC2	ENST00000374231.8 link	c.*31-327G>T		intron_variant	Intron 4 of 4	3		ENSP00000363348.4	V5IRT4
UQCC2	ENST00000606961.1 link	n.2883G>T		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251364

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461708

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

T;T

Eigen

Benign

-0.095

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.84

.;T

M_CAP

Uncertain

0.092

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.40

MutationAssessor

Benign

0.0

N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.16

N;.

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.093

B;B

Vest4

0.30

MutPred

0.30

Loss of MoRF binding (P = 0.0027);Loss of MoRF binding (P = 0.0027);

MVP

0.59

MPC

1.8

ClinPred

0.51

GERP RS

5.0

Varity_R

0.41

gMVP

0.38

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over