Genetic Variant NM_001034841.4:c.1028C>G (chr16-19115489-C-G) – 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.1028C>G(p.Ala343Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,454,326 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000028 ( 0 hom. )

Consequence

ITPRIPL2
NM_001034841.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

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 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=0.054585695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPRIPL2	NM_001034841.4 link	c.1028C>G	p.Ala343Gly	missense_variant	Exon 1 of 1	ENST00000381440.5	NP_001030013.1	Q3MIP1
ITPRIPL2	NR_028028.2 link	n.1010C>G		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ITPRIPL2	ENST00000381440.5 link	c.1028C>G	p.Ala343Gly	missense_variant	Exon 1 of 1	6	NM_001034841.4	ENSP00000370849.3	Q3MIP1
ITPRIPL2	ENST00000566735.1 link	n.1042C>G		non_coding_transcript_exon_variant	Exon 2 of 2	2
ENSG00000261427	ENST00000564808.6 link	n.418+554C>G		intron_variant	Intron 2 of 5	4
ENSG00000261427	ENST00000568526.1 link	n.211+704C>G		intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000123

AC:

AN:

244228

Hom.:

AF XY:

0.00000753

AC XY:

AN XY:

132870

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000892

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1454326

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

723848

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1028C>G (p.A343G) alteration is located in exon 1 (coding exon 1) of the ITPRIPL2 gene. This alteration results from a C to G substitution at nucleotide position 1028, causing the alanine (A) at amino acid position 343 to be replaced by a glycine (G). 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

0.089

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0014

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.60

M_CAP

Benign

0.011

MetaRNN

Benign

0.055

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.90

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.39

REVEL

Benign

0.044

Sift

Benign

0.49

Sift4G

Benign

0.56

Polyphen

0.0010

Vest4

0.044

MutPred

0.31

Gain of loop (P = 0.1069);

MVP

0.030

ClinPred

0.017

GERP RS

4.1

Varity_R

0.041

gMVP

0.29

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