dbSNP rs370538130: ITPRIPL2:p.Ser331Cys (chr16-19115452-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001034841.4(ITPRIPL2):c.991A>T(p.Ser331Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000441 in 1,609,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

ITPRIPL2
NM_001034841.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.136

Publications

0 publications found

Variant links:

Genes affected

ITPRIPL2 (HGNC:27257): (ITPRIP like 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ITPRIPL2 links:

ENSG00000261427 (HGNC:):

ENSG00000261427 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07840866).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034841.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPRIPL2	NM_001034841.4	MANE Select	c.991A>T	p.Ser331Cys	missense	Exon 1 of 1	NP_001030013.1	Q3MIP1
	ITPRIPL2	NR_028028.2		n.973A>T		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITPRIPL2	ENST00000381440.5	TSL:6 MANE Select	c.991A>T	p.Ser331Cys	missense	Exon 1 of 1	ENSP00000370849.3	Q3MIP1
ITPRIPL2	ENST00000566735.1	TSL:2	n.1005A>T		non_coding_transcript_exon	Exon 2 of 2
ENSG00000261427	ENST00000564808.6	TSL:4	n.418+517A>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000648

AC:

AN:

246918

AF XY:

0.0000597

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000977

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.0000439

AC:

AN:

1457104

Hom.:

Cov.:

AF XY:

0.0000469

AC XY:

AN XY:

725140

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.0000671

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48804

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000432

AC:

AN:

1111930

Other (OTH)

AF:

0.0000829

AC:

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41426

American (AMR)

AF:

0.0000655

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000567

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.65

CADD

Benign

3.4

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.0056

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.38

M_CAP

Benign

0.0078

MetaRNN

Benign

0.078

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

PhyloP100

-0.14

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.1

REVEL

Benign

0.0040

Sift

Benign

0.048

Sift4G

Benign

0.083

Polyphen

0.26

Vest4

0.20

MVP

0.040

ClinPred

0.041

GERP RS

-0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.082

gMVP

0.39

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over