20-3209336-G-A

Position:

• chr20-3209336-G-A

Variant summary

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

The NM_001424409.1(ITPA):​c.192+624G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 636,140 control chromosomes in the GnomAD database, including 15,611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3297 hom., cov: 31)
  • Exomes 𝑓: 0.22 (12314 hom.)
• Consequence: ITPA NM_001424409.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.93

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]

ENSG00000289494 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 20-3209336-G-A is Benign according to our data. Variant chr20-3209336-G-A is described in ClinVar as [Benign]. Clinvar id is 1235259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPA	NM_001424409.1	c.192+624G>A		intron_variant			NP_001411338.1
ITPA	NM_001324237.2	c.-272+303G>A		intron_variant			NP_001311166.1
ITPA	NM_001324238.2	c.-275+303G>A		intron_variant			NP_001311167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000289494	ENST00000690923.2	n.141C>T		non_coding_transcript_exon_variant	1/1
ITPA	ENST00000460676.5	n.136+303G>A		intron_variant		3
ITPA	ENST00000483354.5	n.166+303G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31009 AN: 151948 Hom.: 3298 Cov.: 31

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.199

GnomAD4 exome AF: 0.220 AC: 106255 AN: 484074 Hom.: 12314 Cov.: 3 AF XY: 0.221 AC XY: 57217 AN XY: 259454

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.127

Gnomad4 ASJ exome AF: 0.246

Gnomad4 EAS exome AF: 0.155

Gnomad4 SAS exome AF: 0.215

Gnomad4 FIN exome AF: 0.244

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.218

GnomAD4 genome AF: 0.204 AC: 31020 AN: 152066 Hom.: 3297 Cov.: 31 AF XY: 0.203 AC XY: 15079 AN XY: 74324

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.196

Alfa AF: 0.222 Hom.: 944

Bravo AF: 0.193

Asia WGS AF: 0.151 AC: 525 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.34
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6139031; hg19: chr20-3189982;