chr10-104314428-G-T

Position:

chr10-104314428-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000337478.3(ITPRIP):c.1624C>A(p.Gln542Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,611,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ITPRIP
ENST00000337478.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.52

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038239896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPRIP	NM_001272013.2 linkuse as main transcript	c.1624C>A	p.Gln542Lys	missense_variant	2/2	ENST00000337478.3	NP_001258942.1	Q8IWB1
ITPRIP	NM_001272012.2 linkuse as main transcript	c.1624C>A	p.Gln542Lys	missense_variant	2/2		NP_001258941.1	Q8IWB1
ITPRIP	NM_033397.4 linkuse as main transcript	c.1624C>A	p.Gln542Lys	missense_variant	3/3		NP_203755.1	Q8IWB1
ITPRIP	XM_005270257.3 linkuse as main transcript	c.1639C>A	p.Gln547Lys	missense_variant	2/2		XP_005270314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ITPRIP	ENST00000337478.3 linkuse as main transcript	c.1624C>A	p.Gln542Lys	missense_variant	2/2	1	NM_001272013.2	ENSP00000337178.1	Q8IWB1
ITPRIP	ENST00000278071.6 linkuse as main transcript	c.1624C>A	p.Gln542Lys	missense_variant	3/3	1		ENSP00000278071.2	Q8IWB1
ITPRIP	ENST00000358187.2 linkuse as main transcript	c.1624C>A	p.Gln542Lys	missense_variant	2/2	2		ENSP00000350915.2	Q8IWB1
ITPRIP	ENST00000647721.1 linkuse as main transcript	c.1624C>A	p.Gln542Lys	missense_variant	3/3			ENSP00000497746.1	Q8IWB1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

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

GnomAD3 exomes

AF:

0.0000644

AC:

AN:

248578

Hom.:

AF XY:

0.0000594

AC XY:

AN XY:

134736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000465

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:

0.0000123

AC:

AN:

1459318

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

725622

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000381

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:

0.0000166

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000113

ExAC

AF:

0.0000330

AC:

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

Sep 20, 2023

The c.1624C>A (p.Q542K) alteration is located in exon 3 (coding exon 1) of the ITPRIP gene. This alteration results from a C to A substitution at nucleotide position 1624, causing the glutamine (Q) at amino acid position 542 to be replaced by a lysine (K). 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

0.075

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.22

DEOGEN2

Benign

0.074

T;T;T;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.28

T;.;.;.

M_CAP

Benign

0.020

MetaRNN

Benign

0.038

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.38

N;N;N;.

REVEL

Benign

0.077

Sift

Benign

0.66

T;T;T;.

Sift4G

Benign

0.78

T;T;T;.

Polyphen

0.018

B;B;B;B

Vest4

0.19

MutPred

0.18

Gain of methylation at Q542 (P = 0.0062);Gain of methylation at Q542 (P = 0.0062);Gain of methylation at Q542 (P = 0.0062);Gain of methylation at Q542 (P = 0.0062);

MVP

0.030

MPC

0.27

ClinPred

0.064

GERP RS

5.1

Varity_R

0.11

gMVP

0.19

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