dbSNP rs13830: ITPA:c.*123G>A (chr20-3223585-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033453.4(ITPA):c.*123G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0723 in 751,960 control chromosomes in the GnomAD database, including 2,385 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 378 hom., cov: 32)

Exomes 𝑓: 0.075 ( 2007 hom. )

Consequence

ITPA
NM_033453.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.654

Variant links:

Genes affected

ITPA (HGNC:6176): (inosine triphosphatase) This gene encodes an inosine triphosphate pyrophosphohydrolase. The encoded protein hydrolyzes inosine triphosphate and deoxyinosine triphosphate to the monophosphate nucleotide and diphosphate. This protein, which is a member of the HAM1 NTPase protein family, is found in the cytoplasm and acts as a homodimer. Defects in the encoded protein can result in inosine triphosphate pyrophosphorylase deficiency which causes an accumulation of ITP in red blood cells. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

ITPA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 20-3223585-G-A is Benign according to our data. Variant chr20-3223585-G-A is described in ClinVar as [Benign]. Clinvar id is 1168201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPA	NM_033453.4 link	c.*123G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000380113.8	NP_258412.1	Q9BY32-1A0A0S2Z3W7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPA	ENST00000380113.8 link	c.*123G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_033453.4	ENSP00000369456.3		Q9BY32-1

Frequencies

GnomAD3 genomes

AF:

0.0628

AC:

9559

AN:

152136

Hom.:

379

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0441

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.0349

Gnomad ASJ

AF:

0.0611

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.0493

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0704

Gnomad OTH

AF:

0.0593

GnomAD4 exome

AF:

0.0747

AC:

44789

AN:

599706

Hom.:

2007

Cov.:

AF XY:

0.0776

AC XY:

24774

AN XY:

319180

show subpopulations

Gnomad4 AFR exome

AF:

0.0422

Gnomad4 AMR exome

AF:

0.0285

Gnomad4 ASJ exome

AF:

0.0639

Gnomad4 EAS exome

AF:

0.151

Gnomad4 SAS exome

AF:

0.118

Gnomad4 FIN exome

AF:

0.0599

Gnomad4 NFE exome

AF:

0.0687

Gnomad4 OTH exome

AF:

0.0727

GnomAD4 genome

AF:

0.0628

AC:

9557

AN:

152254

Hom.:

378

Cov.:

AF XY:

0.0631

AC XY:

4696

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0440

Gnomad4 AMR

AF:

0.0349

Gnomad4 ASJ

AF:

0.0611

Gnomad4 EAS

AF:

0.174

Gnomad4 SAS

AF:

0.118

Gnomad4 FIN

AF:

0.0493

Gnomad4 NFE

AF:

0.0704

Gnomad4 OTH

AF:

0.0582

Alfa

AF:

0.0671

Hom.:

385

Bravo

AF:

0.0597

Asia WGS

AF:

0.104

AC:

361

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27081565) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Inosine triphosphatase deficiency

Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.95

DANN

Benign

0.71

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