Variant chr2-96326907-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001008949.3(ITPRIPL1):c.276G>C(p.Met92Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000801 in 1,614,240 control chromosomes in the GnomAD database, including 4 homozygotes. 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 0.00069 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00081 ( 3 hom. )

Consequence

ITPRIPL1
NM_001008949.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012882322).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPRIPL1	NM_001008949.3 linkuse as main transcript	c.276G>C	p.Met92Ile	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.276G>C	p.Met92Ile	missense_variant	3/3	1	NM_001008949.3		Q6GPH6-1

Frequencies

GnomAD3 genomes

AF:

0.000690

AC:

105

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000807

AC:

203

AN:

251488

Hom.:

AF XY:

0.000758

AC XY:

103

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000882

Gnomad FIN exome

AF:

0.00152

Gnomad NFE exome

AF:

0.00119

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000813

AC:

1188

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000853

AC XY:

620

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00151

Gnomad4 FIN exome

AF:

0.00174

Gnomad4 NFE exome

AF:

0.000823

Gnomad4 OTH exome

AF:

0.000629

GnomAD4 genome

AF:

0.000689

AC:

105

AN:

152364

Hom.:

Cov.:

AF XY:

0.000698

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00107

Hom.:

Bravo

AF:

0.000540

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000733

AC:

EpiCase

AF:

0.000872

EpiControl

AF:

0.000652

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 09, 2021

The c.300G>C (p.M100I) alteration is located in exon 1 (coding exon 1) of the ITPRIPL1 gene. This alteration results from a G to C substitution at nucleotide position 300, causing the methionine (M) at amino acid position 100 to be replaced by an isoleucine (I). 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

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0098

.;.;T;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.71

T;T;T;T

M_CAP

Benign

0.0032

MetaRNN

Benign

0.013

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;.;L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.9

N;N;N;N

REVEL

Benign

0.079

Sift

Benign

0.063

T;T;T;T

Sift4G

Benign

0.22

T;T;T;T

Polyphen

0.0020, 0.0040

.;.;B;B

Vest4

0.13, 0.11, 0.12

MutPred

0.28

.;.;Loss of solvent accessibility (P = 0.0022);.;

MVP

0.14

MPC

0.16

ClinPred

0.0064

GERP RS

2.9

Varity_R

0.030

gMVP

0.15

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