20-3213196-C-T

Variant names:

• chr20-3213196-C-T
• NM_033453.4:c.94C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033453.4(ITPA):​c.94C>T​(p.Pro32Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P32P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ITPA NM_033453.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.18

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPA	NM_033453.4	c.94C>T	p.Pro32Ser	missense_variant	Exon 2 of 8	ENST00000380113.8	NP_258412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPA	ENST00000380113.8	c.94C>T	p.Pro32Ser	missense_variant	Exon 2 of 8	1	NM_033453.4	ENSP00000369456.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461832 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727222

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

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	0.14
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.81	D;.
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.0039	T
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-5.1	D;D
REVEL	Benign	0.15
Sift	Benign	0.17	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.0030	B;.
Vest4		0.68
MutPred		0.58		Loss of catalytic residue at P32 (P = 0.0258);.;
MVP		0.69
MPC		0.45
ClinPred		0.96	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.50
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.21		Position offset: -27

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: chr20-3193842; COSMIC: COSV66318648; COSMIC: COSV66318648;