Variant chr14-20472290-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.32

Variant links:

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]

PNP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNP	NM_000270.4 linkuse as main transcript	c.12-18A>T		intron_variant		ENST00000361505.10	NP_000261.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNP	ENST00000361505.10 linkuse as main transcript	c.12-18A>T		intron_variant		1	NM_000270.4	ENSP00000354532	P1

Frequencies

GnomAD3 genomes

AF:

0.00371

AC:

565

AN:

152144

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00653

AC XY:

888

AN XY:

135910

show subpopulations

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.:

Cov.:

AF XY:

0.00573

AC XY:

4155

AN XY:

725628

show subpopulations

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.:

Cov.:

AF XY:

0.00392

AC XY:

292

AN XY:

74468

show subpopulations

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.:

Bravo

AF:

0.00314

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over