14-20472290-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000270.4(PNP):c.12-18A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00506 in 1,610,304 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0052 (64 hom.)
• Consequence: PNP NM_000270.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.32

Genes affected

PNP (HGNC:7892): (purine nucleoside phosphorylase) This gene encodes an enzyme which reversibly catalyzes the phosphorolysis of purine nucleosides. The enzyme is trimeric, containing three identical subunits. Mutations which result in nucleoside phosphorylase deficiency result in defective T-cell (cell-mediated) immunity but can also affect B-cell immunity and antibody responses. Neurologic disorders may also be apparent in patients with immune defects. A known polymorphism at aa position 51 that does not affect enzyme activity has been described. A pseudogene has been identified on chromosome 2. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 14-20472290-A-T is Benign according to our data. Variant chr14-20472290-A-T is described in ClinVar as [Benign]. Clinvar id is 138728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-20472290-A-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00371 (565/152262) while in subpopulation SAS AF= 0.0191 (92/4826). AF 95% confidence interval is 0.0159. There are 8 homozygotes in gnomad4. There are 292 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNP	NM_000270.4	c.12-18A>T		intron_variant		ENST00000361505.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNP	ENST00000361505.10	c.12-18A>T		intron_variant		1	NM_000270.4	P1

Frequencies

GnomAD3 genomes AF: 0.00371 AC: 565 AN: 152144 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.000845

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0193

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00535

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00555 AC: 1395 AN: 251462 Hom.: 16 AF XY: 0.00653 AC XY: 888 AN XY: 135910

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.00214

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00152

Gnomad SAS exome AF: 0.0196

Gnomad FIN exome AF: 0.00176

Gnomad NFE exome AF: 0.00543

Gnomad OTH exome AF: 0.00407

GnomAD4 exome AF: 0.00520 AC: 7578 AN: 1458042 Hom.: 64 Cov.: 29 AF XY: 0.00573 AC XY: 4155 AN XY: 725628

Gnomad4 AFR exome AF: 0.00105

Gnomad4 AMR exome AF: 0.00224

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.000680

Gnomad4 SAS exome AF: 0.0195

Gnomad4 FIN exome AF: 0.00185

Gnomad4 NFE exome AF: 0.00476

Gnomad4 OTH exome AF: 0.00501

GnomAD4 genome AF: 0.00371 AC: 565 AN: 152262 Hom.: 8 Cov.: 32 AF XY: 0.00392 AC XY: 292 AN XY: 74468

Gnomad4 AFR AF: 0.000843

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0191

Gnomad4 FIN AF: 0.00170

Gnomad4 NFE AF: 0.00535

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00427 Hom.: 1

Bravo AF: 0.00314

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 31, 2013

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Purine-nucleoside phosphorylase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.047
Dann	Benign	0.69

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: rs117497269; hg19: chr14-20940449;