rs758372914

Positions:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_001378452.1(ITPR1):c.5301C>A(p.Ser1767Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ITPR1
NM_001378452.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.12

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 links:

ITPR1 (HGNC:):

ITPR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ITPR1. . Gene score misZ 5.5951 (greater than the threshold 3.09). Trascript score misZ 6.2026 (greater than threshold 3.09). GenCC has associacion of gene with spinocerebellar ataxia type 15/16, aniridia-cerebellar ataxia-intellectual disability syndrome, spinocerebellar ataxia type 29.

BP4

Computational evidence support a benign effect (MetaRNN=0.16963562).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR1	NM_001378452.1 linkuse as main transcript	c.5301C>A	p.Ser1767Arg	missense_variant	43/62	ENST00000649015.2	NP_001365381.1
ITPR1	NM_001168272.2 linkuse as main transcript	c.5256C>A	p.Ser1752Arg	missense_variant	42/61		NP_001161744.1	Q14643-2
ITPR1	NM_001099952.4 linkuse as main transcript	c.5157C>A	p.Ser1719Arg	missense_variant	40/59		NP_001093422.2	Q14643-3B4DER3Q59H91
ITPR1	NM_002222.7 linkuse as main transcript	c.5112C>A	p.Ser1704Arg	missense_variant	39/58		NP_002213.5	Q14643-4B4DER3B4DGH1Q59H91

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ITPR1	ENST00000649015.2 linkuse as main transcript	c.5301C>A	p.Ser1767Arg	missense_variant	43/62		NM_001378452.1	ENSP00000497605.1	Q14643-1
ITPR1	ENST00000354582.12 linkuse as main transcript	c.5277C>A	p.Ser1759Arg	missense_variant	43/62	5		ENSP00000346595.8	A0A3F2YNW8
ITPR1	ENST00000648266.1 linkuse as main transcript	c.5274C>A	p.Ser1758Arg	missense_variant	43/62			ENSP00000498014.1	A0A3B3IU04
ITPR1	ENST00000650294.1 linkuse as main transcript	c.5259C>A	p.Ser1753Arg	missense_variant	42/61			ENSP00000498056.1	A0A3B3ITU8
ITPR1	ENST00000443694.5 linkuse as main transcript	c.5256C>A	p.Ser1752Arg	missense_variant	42/61	1		ENSP00000401671.2	Q14643-2
ITPR1	ENST00000648309.1 linkuse as main transcript	c.5229C>A	p.Ser1743Arg	missense_variant	40/59			ENSP00000497026.1	Q14643-5
ITPR1	ENST00000357086.10 linkuse as main transcript	c.5157C>A	p.Ser1719Arg	missense_variant	40/59	1		ENSP00000349597.4	Q14643-3
ITPR1	ENST00000456211.8 linkuse as main transcript	c.5112C>A	p.Ser1704Arg	missense_variant	39/58	1		ENSP00000397885.2	Q14643-4
ITPR1	ENST00000648038.1 linkuse as main transcript	c.3063C>A	p.Ser1021Arg	missense_variant	23/42			ENSP00000497872.1	A0A3B3ITQ1
ITPR1	ENST00000648431.1 linkuse as main transcript	c.2601C>A	p.Ser867Arg	missense_variant	21/39			ENSP00000498149.1	A0A3B3IU05
ITPR1	ENST00000648212.1 linkuse as main transcript	c.2208C>A	p.Ser736Arg	missense_variant	19/39			ENSP00000498022.1	A0A3B3IU13

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249120

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135164

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461672

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000468

Hom.:

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Athena Diagnostics

May 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.46

.;.;.;.;.;.;T;.;.;.;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.96

D;D;D;D;D;D;D;D;.;D;D

M_CAP

Benign

0.026

MetaRNN

Benign

0.17

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.41

MutationAssessor

Benign

1.6

.;.;.;.;.;.;L;.;.;.;.

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.5

N;N;N;N;.;.;.;.;N;.;.

REVEL

Uncertain

0.40

Sift

Benign

0.35

T;T;T;T;.;.;.;.;T;.;.

Sift4G

Benign

0.50

T;T;.;T;.;.;.;.;T;.;.

Polyphen

0.0020

.;.;.;.;.;.;B;.;.;.;.

Vest4

0.57

MutPred

0.21

.;.;.;.;.;.;Gain of MoRF binding (P = 0.0152);.;.;.;.;

MVP

0.96

MPC

0.19

ClinPred

0.27

GERP RS

4.7

Varity_R

0.18

gMVP

0.56

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over