20-3209393-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000690923.2(ENSG00000289494):n.84G>C variant causes a non coding transcript exon 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: ENST00000690923.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.54

Genes affected

(HGNC:):

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 -14 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_single_submitter, 1 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	UniProt
ITPA	NM_001324237.2	c.-272+360C>G		intron_variant
ITPA	NM_001324238.2	c.-275+360C>G		intron_variant
ITPA	XM_047440139.1	c.192+681C>G		intron_variant

Ensembl

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

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

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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;