rs13830

Variant names:

• chr20-3223585-G-A
• rs13830
• NM_033453.4:c.*123G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-3223585-G-A
• chr20-3223585-G-C

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: -0.654
• Publications: 24 publications found

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 Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 35

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• inosine triphosphatase deficiency

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033453.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPA	NM_033453.4	MANE Select	c.*123G>A		3_prime_UTR	Exon 8 of 8	NP_258412.1	A0A0S2Z3W7
	ITPA	NM_001424408.1		c.*38G>A		3_prime_UTR	Exon 9 of 9	NP_001411337.1
	ITPA	NM_001424409.1		c.*123G>A		3_prime_UTR	Exon 9 of 9	NP_001411338.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPA	ENST00000380113.8	TSL:1 MANE Select	c.*123G>A		3_prime_UTR	Exon 8 of 8	ENSP00000369456.3	Q9BY32-1
	ITPA	ENST00000455664.6	TSL:1	c.*123G>A		3_prime_UTR	Exon 8 of 8	ENSP00000413282.1	Q9BY32-2
	ITPA	ENST00000399838.3	TSL:1	c.*123G>A		3_prime_UTR	Exon 6 of 6	ENSP00000382732.3	Q9BY32-3

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

African (AFR) AF: 0.0422 AC: 705 AN: 16688

American (AMR) AF: 0.0285 AC: 975 AN: 34234

Ashkenazi Jewish (ASJ) AF: 0.0639 AC: 1254 AN: 19610

East Asian (EAS) AF: 0.151 AC: 4829 AN: 31962

South Asian (SAS) AF: 0.118 AC: 7317 AN: 61836

European-Finnish (FIN) AF: 0.0599 AC: 2020 AN: 33740

Middle Eastern (MID) AF: 0.0600 AC: 153 AN: 2550

European-Non Finnish (NFE) AF: 0.0687 AC: 25219 AN: 367236

Other (OTH) AF: 0.0727 AC: 2317 AN: 31850

GnomAD4 genome AF: 0.0628 AC: 9557 AN: 152254 Hom.: 378 Cov.: 32 AF XY: 0.0631 AC XY: 4696 AN XY: 74462

African (AFR) AF: 0.0440 AC: 1829 AN: 41552

American (AMR) AF: 0.0349 AC: 534 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0611 AC: 212 AN: 3472

East Asian (EAS) AF: 0.174 AC: 901 AN: 5164

South Asian (SAS) AF: 0.118 AC: 568 AN: 4822

European-Finnish (FIN) AF: 0.0493 AC: 523 AN: 10618

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0704 AC: 4790 AN: 67996

Other (OTH) AF: 0.0582 AC: 123 AN: 2112

Alfa AF: 0.0657 Hom.: 486

Bravo AF: 0.0597

Asia WGS AF: 0.104 AC: 361 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Inosine triphosphatase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.95
DANN	Benign	0.71
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13830; hg19: chr20-3204231;