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GeneBe

10-104314878-G-A

Variant summary

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

The NM_001272013.2(ITPRIP):​c.1174C>T​(p.Leu392Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,613,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ITPRIP
NM_001272013.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.31
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]

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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=0.17318177).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ITPRIPNM_001272013.2 linkuse as main transcriptc.1174C>T p.Leu392Phe missense_variant 2/2 ENST00000337478.3
ITPRIPNM_001272012.2 linkuse as main transcriptc.1174C>T p.Leu392Phe missense_variant 2/2
ITPRIPNM_033397.4 linkuse as main transcriptc.1174C>T p.Leu392Phe missense_variant 3/3
ITPRIPXM_005270257.3 linkuse as main transcriptc.1189C>T p.Leu397Phe missense_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ITPRIPENST00000337478.3 linkuse as main transcriptc.1174C>T p.Leu392Phe missense_variant 2/21 NM_001272013.2 P1
ITPRIPENST00000278071.6 linkuse as main transcriptc.1174C>T p.Leu392Phe missense_variant 3/31 P1
ITPRIPENST00000358187.2 linkuse as main transcriptc.1174C>T p.Leu392Phe missense_variant 2/22 P1
ITPRIPENST00000647721.1 linkuse as main transcriptc.1174C>T p.Leu392Phe missense_variant 3/3 P1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152194
Hom.:
0
Cov.:
33
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:
0.000386
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:
0.0000160
AC:
4
AN:
249674
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135396
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000218
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:
0.00000547
AC:
8
AN:
1461436
Hom.:
0
Cov.:
34
AF XY:
0.00000688
AC XY:
5
AN XY:
727040
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000202
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152194
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264
ExAC
AF:
0.0000247
AC:
3

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 submitterclinical testingAmbry GeneticsMay 18, 2023The c.1174C>T (p.L392F) alteration is located in exon 3 (coding exon 1) of the ITPRIP gene. This alteration results from a C to T substitution at nucleotide position 1174, causing the leucine (L) at amino acid position 392 to be replaced by a phenylalanine (F). 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
0.13
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.084
T;T;T;T
Eigen
Benign
0.066
Eigen_PC
Benign
0.12
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.62
T;.;.;.
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.17
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L;L;L;L
MutationTaster
Benign
0.99
D;D;D
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-1.5
N;N;N;.
REVEL
Benign
0.12
Sift
Benign
0.035
D;D;D;.
Sift4G
Benign
0.089
T;T;T;.
Polyphen
0.41
B;B;B;B
Vest4
0.18
MutPred
0.59
Loss of stability (P = 0.1076);Loss of stability (P = 0.1076);Loss of stability (P = 0.1076);Loss of stability (P = 0.1076);
MVP
0.088
MPC
0.44
ClinPred
0.19
T
GERP RS
4.0
Varity_R
0.12
gMVP
0.38

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.

Other links and lift over

dbSNP: rs756512937; hg19: chr10-106074636; API