Variant 14-20474585-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000270.4(PNP):c.285+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,609,246 control chromosomes in the GnomAD database, including 34,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4220 hom., cov: 32)

Exomes 𝑓: 0.20 ( 30478 hom. )

Consequence

PNP
NM_000270.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.140

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=-0.82).

BP6

Variant 14-20474585-A-G is Benign according to our data. Variant chr14-20474585-A-G is described in ClinVar as [Benign]. Clinvar id is 312730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-20474585-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNP	NM_000270.4 link	c.285+10A>G		intron_variant	Intron 3 of 5	ENST00000361505.10	NP_000261.2	P00491V9HWH6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNP	ENST00000361505.10 link	c.285+10A>G		intron_variant	Intron 3 of 5	1	NM_000270.4	ENSP00000354532.6		P00491

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34319

AN:

151960

Hom.:

4209

Cov.:

show subpopulations

Gnomad AFR

AF:

0.315

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.184

Gnomad ASJ

AF:

0.188

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.146

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.205

Gnomad OTH

AF:

0.208

GnomAD3 exomes

AF:

0.189

AC:

47543

AN:

251404

Hom.:

4930

AF XY:

0.188

AC XY:

25539

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.318

Gnomad AMR exome

AF:

0.145

Gnomad ASJ exome

AF:

0.186

Gnomad EAS exome

AF:

0.107

Gnomad SAS exome

AF:

0.158

Gnomad FIN exome

AF:

0.185

Gnomad NFE exome

AF:

0.206

Gnomad OTH exome

AF:

0.199

GnomAD4 exome

AF:

0.201

AC:

292589

AN:

1457168

Hom.:

30478

Cov.:

AF XY:

0.199

AC XY:

144582

AN XY:

725252

show subpopulations

Gnomad4 AFR exome

AF:

0.330

Gnomad4 AMR exome

AF:

0.153

Gnomad4 ASJ exome

AF:

0.190

Gnomad4 EAS exome

AF:

0.132

Gnomad4 SAS exome

AF:

0.158

Gnomad4 FIN exome

AF:

0.184

Gnomad4 NFE exome

AF:

0.205

Gnomad4 OTH exome

AF:

0.204

GnomAD4 genome

AF:

0.226

AC:

34367

AN:

152078

Hom.:

4220

Cov.:

AF XY:

0.222

AC XY:

16484

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.316

Gnomad4 AMR

AF:

0.184

Gnomad4 ASJ

AF:

0.188

Gnomad4 EAS

AF:

0.117

Gnomad4 SAS

AF:

0.146

Gnomad4 FIN

AF:

0.183

Gnomad4 NFE

AF:

0.205

Gnomad4 OTH

AF:

0.207

Alfa

AF:

0.212

Hom.:

2927

Bravo

AF:

0.231

Asia WGS

AF:

0.139

AC:

487

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Purine-nucleoside phosphorylase deficiency

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 25, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:3

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 36% of patients studied by a panel of primary immunodeficiencies. Number of patients: 34. Only high quality variants are reported. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.7

DANN

Benign

0.47

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