3-4814550-G-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001378452.1(ITPR1):c.7689G>C(p.Lys2563Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K2563K) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 24)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ITPR1
NM_001378452.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.44

Publications

31 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:

ENSG00000235978 (HGNC:):

ENSG00000235978 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3333463).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR1	NM_001378452.1 link	c.7689G>C	p.Lys2563Asn	missense_variant	Exon 58 of 62	ENST00000649015.2	NP_001365381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ITPR1	ENST00000649015.2 link	c.7689G>C	p.Lys2563Asn	missense_variant	Exon 58 of 62		NM_001378452.1	ENSP00000497605.1
ITPR1	ENST00000354582.12 link	c.7665G>C	p.Lys2555Asn	missense_variant	Exon 58 of 62	5		ENSP00000346595.8
ITPR1	ENST00000648266.1 link	c.7662G>C	p.Lys2554Asn	missense_variant	Exon 58 of 62			ENSP00000498014.1
ITPR1	ENST00000650294.1 link	c.7647G>C	p.Lys2549Asn	missense_variant	Exon 57 of 61			ENSP00000498056.1
ITPR1	ENST00000443694.5 link	c.7644G>C	p.Lys2548Asn	missense_variant	Exon 57 of 61	1		ENSP00000401671.2
ITPR1	ENST00000648309.1 link	c.7617G>C	p.Lys2539Asn	missense_variant	Exon 55 of 59			ENSP00000497026.1
ITPR1	ENST00000357086.10 link	c.7545G>C	p.Lys2515Asn	missense_variant	Exon 55 of 59	1		ENSP00000349597.4
ITPR1	ENST00000456211.8 link	c.7500G>C	p.Lys2500Asn	missense_variant	Exon 54 of 58	1		ENSP00000397885.2
ITPR1	ENST00000648038.1 link	c.5451G>C	p.Lys1817Asn	missense_variant	Exon 38 of 42			ENSP00000497872.1
ITPR1	ENST00000648431.1 link	c.4866G>C	p.Lys1622Asn	missense_variant	Exon 35 of 39			ENSP00000498149.1
ITPR1	ENST00000648212.1 link	c.4629G>C	p.Lys1543Asn	missense_variant	Exon 35 of 39			ENSP00000498022.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149262

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000403

AC:

AN:

248248

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:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.92e-7

AC:

AN:

1445478

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718850

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32746

American (AMR)

AF:

0.00

AC:

AN:

44028

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25466

East Asian (EAS)

AF:

0.00

AC:

AN:

38708

South Asian (SAS)

AF:

0.00

AC:

AN:

86070

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51922

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5530

European-Non Finnish (NFE)

AF:

9.08e-7

AC:

AN:

1101802

Other (OTH)

AF:

0.00

AC:

AN:

59206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

149262

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72584

African (AFR)

AF:

0.00

AC:

AN:

40348

American (AMR)

AF:

0.00

AC:

AN:

14902

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

4970

South Asian (SAS)

AF:

0.00

AC:

AN:

4700

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10066

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67566

Other (OTH)

AF:

0.00

AC:

AN:

2044

Alfa

AF:

0.00

Hom.:

59277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Pathogenic

0.82

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

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.92

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

M_CAP

Benign

0.085

MetaRNN

Benign

0.33

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

MetaSVM

Uncertain

0.38

MutationAssessor

Benign

1.4

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

PhyloP100

1.4

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-2.4

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

REVEL

Uncertain

0.29

Sift

Benign

0.42

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

Sift4G

Benign

0.39

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

Polyphen

0.24, 0.019

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

Vest4

0.52

MutPred

0.48

.;.;.;.;.;.;.;Loss of methylation at K2563 (P = 0.0018);.;.;.;

MVP

0.82

MPC

2.1

ClinPred

0.52

GERP RS

3.1

PromoterAI

-0.19

Neutral

(source)

Varity_R

0.25

gMVP

0.96

Mutation Taster

=39/61

disease causing

(source)

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

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over