Variant chr2-96327598-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001008949.3(ITPRIPL1):c.967C>T(p.Arg323Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000758 in 1,608,736 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R323Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

ITPRIPL1
NM_001008949.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.30

Variant links:

Genes affected

ITPRIPL1 (HGNC:29371): (ITPRIP like 1) Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ITPRIPL1 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=0.10896447).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPRIPL1	NM_001008949.3 linkuse as main transcript	c.967C>T	p.Arg323Trp	missense_variant	3/3	ENST00000439118.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPRIPL1	ENST00000439118.3 linkuse as main transcript	c.967C>T	p.Arg323Trp	missense_variant	3/3	1	NM_001008949.3		Q6GPH6-1
ITPRIPL1	ENST00000420728.1 linkuse as main transcript	c.1063C>T	p.Arg355Trp	missense_variant	2/2	2
ITPRIPL1	ENST00000361124.5 linkuse as main transcript	c.991C>T	p.Arg331Trp	missense_variant	1/1				Q6GPH6-2
ITPRIPL1	ENST00000536814.1 linkuse as main transcript	c.943C>T	p.Arg315Trp	missense_variant	2/2	3		P1	Q6GPH6-3

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000942

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000899

AC:

AN:

244826

Hom.:

AF XY:

0.0000755

AC XY:

AN XY:

132452

show subpopulations

Gnomad AFR exome

AF:

0.000871

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:

0.0000722

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000522

AC:

AN:

1456492

Hom.:

Cov.:

AF XY:

0.0000442

AC XY:

AN XY:

724216

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000302

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000939

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000824

Hom.:

Bravo

AF:

0.000317

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000115

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

Aug 02, 2023

The c.991C>T (p.R331W) alteration is located in exon 1 (coding exon 1) of the ITPRIPL1 gene. This alteration results from a C to T substitution at nucleotide position 991, causing the arginine (R) at amino acid position 331 to be replaced by a tryptophan (W). 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

0.11

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.11

.;T;.

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.77

T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

.;M;.

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.2

D;D;D

REVEL

Benign

0.19

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

1.0, 1.0

.;D;D

Vest4

0.54

MVP

0.48

MPC

0.51

ClinPred

0.27

GERP RS

4.8

Varity_R

0.16

gMVP

0.58

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