Genetic Variant ITPRIPL1:p.Tyr21Phe (chr2-96326693-A-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_001008949.3(ITPRIPL1):c.62A>T(p.Tyr21Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y21C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

ITPRIPL1
NM_001008949.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.24

Publications

1 publications found

Variant links:

Genes affected

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

ITPRIPL1 links:

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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=0.1853857).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008949.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITPRIPL1	NM_001008949.3	MANE Select	c.62A>T	p.Tyr21Phe	missense	Exon 3 of 3	NP_001008949.1	Q6GPH6-1
ITPRIPL1	NM_178495.6		c.86A>T	p.Tyr29Phe	missense	Exon 1 of 1	NP_848590.3
ITPRIPL1	NM_001163523.2		c.38A>T	p.Tyr13Phe	missense	Exon 2 of 2	NP_001156995.1	Q6GPH6-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITPRIPL1	ENST00000439118.3	TSL:1 MANE Select	c.62A>T	p.Tyr21Phe	missense	Exon 3 of 3	ENSP00000389308.2	Q6GPH6-1
ITPRIPL1	ENST00000420728.1	TSL:2	c.155A>T	p.Tyr52Phe	missense	Exon 2 of 2	ENSP00000396552.1	H7C0T2
ITPRIPL1	ENST00000361124.5	TSL:6	c.86A>T	p.Tyr29Phe	missense	Exon 1 of 1	ENSP00000355121.4	Q6GPH6-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74354

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000241

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.013

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.83

M_CAP

Benign

0.0042

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

3.2

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.11

Sift

Benign

0.20

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.46

MutPred

0.41

Gain of helix (P = 0.1736)

MVP

0.15

MPC

0.61

ClinPred

0.75

GERP RS

4.9

PromoterAI

-0.0017

Neutral

(source)

Varity_R

0.068

gMVP

0.13

Mutation Taster

=98/2

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over