20-3207087-T-C

Variant names:

• chr20-3207087-T-C
• rs6139030
• NM_001424409.1:c.-125-1309T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001424409.1(ITPA):​c.-125-1309T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0865 in 152,138 control chromosomes in the GnomAD database, including 655 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.086 (655 hom., cov: 31)
• Consequence: ITPA NM_001424409.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.246
• Publications: 31 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

ENSG00000303521 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001424409.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPA	NM_001424409.1		c.-125-1309T>C		intron	N/A	NP_001411338.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000303521	ENST00000795247.1		n.248-1147T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0865 AC: 13143 AN: 152020 Hom.: 654 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.0441

Gnomad ASJ AF: 0.0720

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0488

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0732

Gnomad OTH AF: 0.0776

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0865 AC: 13155 AN: 152138 Hom.: 655 Cov.: 31 AF XY: 0.0860 AC XY: 6397 AN XY: 74370

African (AFR) AF: 0.119 AC: 4942 AN: 41514

American (AMR) AF: 0.0440 AC: 672 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0720 AC: 250 AN: 3470

East Asian (EAS) AF: 0.181 AC: 932 AN: 5148

South Asian (SAS) AF: 0.128 AC: 618 AN: 4822

European-Finnish (FIN) AF: 0.0488 AC: 517 AN: 10600

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0732 AC: 4976 AN: 67998

Other (OTH) AF: 0.0763 AC: 161 AN: 2110

Alfa AF: 0.0795 Hom.: 2121

Bravo AF: 0.0856

Asia WGS AF: 0.111 AC: 383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.9
DANN	Benign	0.62
PhyloP100		0.25

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6139030; hg19: chr20-3187733;