Genetic Variant ITPRIPL2:p.Ala41Ser (chr16-19114582-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001034841.4(ITPRIPL2):c.121G>T(p.Ala41Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ITPRIPL2
NM_001034841.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0500

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04433179).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPRIPL2	NM_001034841.4 link	c.121G>T	p.Ala41Ser	missense_variant	Exon 1 of 1	ENST00000381440.5	NP_001030013.1	Q3MIP1
ITPRIPL2	NR_028028.2 link	n.162-59G>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ITPRIPL2	ENST00000381440.5 link	c.121G>T	p.Ala41Ser	missense_variant	Exon 1 of 1	6	NM_001034841.4	ENSP00000370849.3	Q3MIP1
ENSG00000261427	ENST00000564808.6 link	n.124-59G>T		intron_variant	Intron 1 of 5	4
ITPRIPL2	ENST00000566735.1 link	n.194-59G>T		intron_variant	Intron 1 of 1	2
ENSG00000261427	ENST00000568526.1 link	n.67-59G>T		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1416914

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

701056

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.121G>T (p.A41S) alteration is located in exon 1 (coding exon 1) of the ITPRIPL2 gene. This alteration results from a G to T substitution at nucleotide position 121, causing the alanine (A) at amino acid position 41 to be replaced by a serine (S). 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

0.071

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.00062

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.44

M_CAP

Benign

0.0053

MetaRNN

Benign

0.044

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.34

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.25

REVEL

Benign

0.029

Sift

Benign

0.11

Sift4G

Benign

0.42

Polyphen

0.0

Vest4

0.028

MutPred

0.13

Gain of disorder (P = 0.0499);

MVP

0.048

ClinPred

0.028

GERP RS

1.2

Varity_R

0.048

gMVP

0.11

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over