20-3209600-G-A

Variant names:

• chr20-3209600-G-A
• NM_033453.4:c.49G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_033453.4(ITPA):​c.49G>A​(p.Ala17Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,784 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ITPA NM_033453.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.34

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39848262).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPA	NM_033453.4	c.49G>A	p.Ala17Thr	missense_variant	Exon 1 of 8	ENST00000380113.8	NP_258412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPA	ENST00000380113.8	c.49G>A	p.Ala17Thr	missense_variant	Exon 1 of 8	1	NM_033453.4	ENSP00000369456.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461784 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727184

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.77	D;.
Eigen	Benign	-0.098
Eigen_PC	Benign	-0.0050
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.94	D;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Pathogenic	3.0	M;M
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Uncertain	0.42
Sift	Benign	0.052	T;D
Sift4G	Benign	0.12	T;T
Polyphen		0.079	B;.
Vest4		0.47
MutPred		0.47		Loss of MoRF binding (P = 0.0954);Loss of MoRF binding (P = 0.0954);
MVP		0.57
MPC		0.31
ClinPred		0.99	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.76
gMVP		0.081

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-3190246;