10-104315222-G-C

Variant summary

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

The NM_001272013.2(ITPRIP):c.830C>G(p.Ala277Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 0.0000027 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ITPRIP
NM_001272013.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.40

Variant links:

Genes affected

ITPRIP (HGNC:29370): (inositol 1,4,5-trisphosphate receptor interacting protein) This gene encodes a membrane-associated protein that binds the inositol 1,4,5-trisphosphate receptor (ITPR). The encoded protein enhances the sensitivity of ITPR to intracellular calcium signaling. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

ITPRIP links:

Genome browser will be placed here

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=0.0693503).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ITPRIP	NM_001272013.2 linkuse as main transcript	c.830C>G	p.Ala277Gly	missense_variant	2/2	ENST00000337478.3
ITPRIP	NM_001272012.2 linkuse as main transcript	c.830C>G	p.Ala277Gly	missense_variant	2/2
ITPRIP	NM_033397.4 linkuse as main transcript	c.830C>G	p.Ala277Gly	missense_variant	3/3
ITPRIP	XM_005270257.3 linkuse as main transcript	c.845C>G	p.Ala282Gly	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ITPRIP	ENST00000337478.3 linkuse as main transcript	c.830C>G	p.Ala277Gly	missense_variant	2/2	1	NM_001272013.2	P1
ITPRIP	ENST00000278071.6 linkuse as main transcript	c.830C>G	p.Ala277Gly	missense_variant	3/3	1		P1
ITPRIP	ENST00000358187.2 linkuse as main transcript	c.830C>G	p.Ala277Gly	missense_variant	2/2	2		P1
ITPRIP	ENST00000647721.1 linkuse as main transcript	c.830C>G	p.Ala277Gly	missense_variant	3/3			P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152190

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

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

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461500

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727034

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:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000657

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 17, 2023

The c.830C>G (p.A277G) alteration is located in exon 3 (coding exon 1) of the ITPRIP gene. This alteration results from a C to G substitution at nucleotide position 830, causing the alanine (A) at amino acid position 277 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

Cadd

Benign

0.019

Dann

Benign

0.57

DEOGEN2

Benign

0.13

T;T;T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.34

T;.;.;.

M_CAP

Benign

0.0027

MetaRNN

Benign

0.069

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;M;M;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.73

N;N;N;.

REVEL

Benign

0.021

Sift

Benign

0.37

T;T;T;.

Sift4G

Benign

0.18

T;T;T;.

Polyphen

0.0

B;B;B;B

Vest4

0.083

MutPred

0.20

Gain of disorder (P = 0.0511);Gain of disorder (P = 0.0511);Gain of disorder (P = 0.0511);Gain of disorder (P = 0.0511);

MVP

0.014

MPC

0.21

ClinPred

0.046

GERP RS

-10

Varity_R

0.022

gMVP

0.22

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