20-3209393-C-G

Position:

• chr20-3209393-C-G

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+681C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 739,010 control chromosomes in the GnomAD database, including 20,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3435 hom., cov: 32)
  • Exomes 𝑓: 0.23 (17353 hom.)
• Consequence: ITPA NM_001424409.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.54

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=-0.85).
• BP6: Variant 20-3209393-C-G is Benign according to our data. Variant chr20-3209393-C-G is described in ClinVar as [Benign]. Clinvar id is 1251484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPA	NM_001424409.1	c.192+681C>G		intron_variant			NP_001411338.1
ITPA	NM_001324237.2	c.-272+360C>G		intron_variant			NP_001311166.1
ITPA	NM_001324238.2	c.-275+360C>G		intron_variant			NP_001311167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000289494	ENST00000690923.2	n.84G>C		non_coding_transcript_exon_variant	1/1
ITPA	ENST00000460676.5	n.136+360C>G		intron_variant		3
ITPA	ENST00000483354.5	n.166+360C>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31203 AN: 151974 Hom.: 3428 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.233 AC: 136605 AN: 586918 Hom.: 17353 Cov.: 7 AF XY: 0.241 AC XY: 75832 AN XY: 314606

Gnomad4 AFR exome AF: 0.160

Gnomad4 AMR exome AF: 0.228

Gnomad4 ASJ exome AF: 0.210

Gnomad4 EAS exome AF: 0.317

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.215

Gnomad4 OTH exome AF: 0.224

GnomAD4 genome AF: 0.205 AC: 31235 AN: 152092 Hom.: 3435 Cov.: 32 AF XY: 0.205 AC XY: 15239 AN XY: 74328

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.236

Alfa AF: 0.198 Hom.: 395

Bravo AF: 0.206

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 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.54

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: rs45620433; hg19: chr20-3190039;