Genetic Variant ITPRIPL2:p.Pro49Leu (chr16-19114607-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001034841.4(ITPRIPL2):c.146C>T(p.Pro49Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000379 in 1,583,966 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 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

ITPRIPL2
NM_001034841.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.27

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18004468).

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.146C>T	p.Pro49Leu	missense	Exon 1 of 1	NP_001030013.1	Q3MIP1
	ITPRIPL2	NR_028028.2		n.162-34C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITPRIPL2	ENST00000381440.5	TSL:6 MANE Select	c.146C>T	p.Pro49Leu	missense	Exon 1 of 1	ENSP00000370849.3	Q3MIP1
ENSG00000261427	ENST00000564808.6	TSL:4	n.124-34C>T		intron	N/A
ITPRIPL2	ENST00000566735.1	TSL:2	n.194-34C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000431

AC:

AN:

208878

AF XY:

0.0000525

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000131

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000429

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000391

AC:

AN:

1431770

Hom.:

Cov.:

AF XY:

0.0000479

AC XY:

AN XY:

710524

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32966

American (AMR)

AF:

0.000121

AC:

AN:

41324

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24258

East Asian (EAS)

AF:

0.00

AC:

AN:

39388

South Asian (SAS)

AF:

0.0000488

AC:

AN:

81992

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45776

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5660

European-Non Finnish (NFE)

AF:

0.0000418

AC:

AN:

1101154

Other (OTH)

AF:

0.0000169

AC:

AN:

59252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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:

0.0000263

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41450

American (AMR)

AF:

0.0000654

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

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:

0.0000427

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000414

AC:

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

0.15

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0043

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.70

M_CAP

Benign

0.059

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

1.3

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.5

REVEL

Benign

0.10

Sift

Benign

0.18

Sift4G

Uncertain

0.033

Polyphen

0.90

Vest4

0.35

MutPred

0.39

Gain of helix (P = 0.0078)

MVP

0.36

ClinPred

0.075

GERP RS

3.5

Varity_R

0.076

gMVP

0.41

Mutation Taster

=77/23

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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