3-4733168-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001378452.1(ITPR1):c.5301C>G(p.Ser1767Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,672 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ITPR1
NM_001378452.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.12

Publications

0 publications found

Variant links:

Genes affected

ITPR1 (HGNC:6180): (inositol 1,4,5-trisphosphate receptor type 1) This gene encodes an intracellular receptor for inositol 1,4,5-trisphosphate. Upon stimulation by inositol 1,4,5-trisphosphate, this receptor mediates calcium release from the endoplasmic reticulum. Mutations in this gene cause spinocerebellar ataxia type 15, a disease associated with an heterogeneous group of cerebellar disorders. Multiple transcript variants have been identified for this gene. [provided by RefSeq, Nov 2009]

ITPR1 Gene-Disease associations (from GenCC):

aniridia-cerebellar ataxia-intellectual disability syndrome
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Genomics England PanelApp, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen
spinocerebellar ataxia type 29
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet
spinocerebellar ataxia type 15/16
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ITPR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17495382).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378452.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ITPR1	NM_001378452.1	MANE Select	c.5301C>G	p.Ser1767Arg	missense	Exon 43 of 62	NP_001365381.1
ITPR1	NM_001168272.2		c.5256C>G	p.Ser1752Arg	missense	Exon 42 of 61	NP_001161744.1
ITPR1	NM_001099952.4		c.5157C>G	p.Ser1719Arg	missense	Exon 40 of 59	NP_001093422.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ITPR1	ENST00000649015.2	MANE Select	c.5301C>G	p.Ser1767Arg	missense	Exon 43 of 62	ENSP00000497605.1
ITPR1	ENST00000354582.12	TSL:5	c.5277C>G	p.Ser1759Arg	missense	Exon 43 of 62	ENSP00000346595.8
ITPR1	ENST00000648266.1		c.5274C>G	p.Ser1758Arg	missense	Exon 43 of 62	ENSP00000498014.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

249120

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461672

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727122

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111844

Other (OTH)

AF:

0.00

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.060

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.46

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.025

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.41

MutationAssessor

Benign

1.6

PhyloP100

2.1

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.40

Sift

Benign

0.35

Sift4G

Benign

0.50

Polyphen

0.0020

Vest4

0.57

MutPred

0.21

Gain of MoRF binding (P = 0.0152)

MVP

0.96

MPC

0.19

ClinPred

0.23

GERP RS

4.7

Varity_R

0.18

gMVP

0.56

Mutation Taster

=65/35

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over