rs13830

chr20-3223585-G-Achr20-3223585-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.654

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]

ACMG classification

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/exons	MANE	UniProt
ITPA	NM_033453.4	c.*123G>A		3_prime_UTR_variant	8/8	ENST00000380113.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPA	ENST00000380113.8	c.*123G>A		3_prime_UTR_variant	8/8	1	NM_033453.4	P1

Frequencies

GnomAD3 genomes AF: 0.0628 AC: 9559 AN: 152136 Hom.: 379 Cov.: 32

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.: 7 AF XY: 0.0776 AC XY: 24774 AN XY: 319180

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.: 32 AF XY: 0.0631 AC XY: 4696 AN XY: 74462

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

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

Inosine triphosphatase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 19, 2024

- -

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

Other links and lift over

dbSNP: rs13830; hg19: chr20-3204231;