rs1049564

Positions:

chr14-20472447-G-A

Variant summary

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

The NM_000270.4(PNP):c.151G>A(p.Gly51Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,610,040 control chromosomes in the GnomAD database, including 28,649 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3257 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25392 hom. )

Consequence

PNP
NM_000270.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 1.61

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 (MetaRNN=0.0010126531).

BP6

Variant 14-20472447-G-A is Benign according to our data. Variant chr14-20472447-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 13992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-20472447-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNP	NM_000270.4 linkuse as main transcript	c.151G>A	p.Gly51Ser	missense_variant	2/6	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.151G>A	p.Gly51Ser	missense_variant	2/6	1	NM_000270.4	ENSP00000354532	P1

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

31071

AN:

152040

Hom.:

3248

Cov.:

show subpopulations

Gnomad AFR

AF:

0.255

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.201

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.141

Gnomad FIN

AF:

0.159

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.192

GnomAD3 exomes

AF:

0.191

AC:

48099

AN:

251310

Hom.:

4752

AF XY:

0.187

AC XY:

25440

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.254

Gnomad AMR exome

AF:

0.235

Gnomad ASJ exome

AF:

0.200

Gnomad EAS exome

AF:

0.193

Gnomad SAS exome

AF:

0.154

Gnomad FIN exome

AF:

0.165

Gnomad NFE exome

AF:

0.183

Gnomad OTH exome

AF:

0.194

GnomAD4 exome

AF:

0.183

AC:

267373

AN:

1457882

Hom.:

25392

Cov.:

AF XY:

0.182

AC XY:

132081

AN XY:

725496

show subpopulations

Gnomad4 AFR exome

AF:

0.262

Gnomad4 AMR exome

AF:

0.234

Gnomad4 ASJ exome

AF:

0.205

Gnomad4 EAS exome

AF:

0.209

Gnomad4 SAS exome

AF:

0.152

Gnomad4 FIN exome

AF:

0.164

Gnomad4 NFE exome

AF:

0.181

Gnomad4 OTH exome

AF:

0.189

GnomAD4 genome

AF:

0.205

AC:

31118

AN:

152158

Hom.:

3257

Cov.:

AF XY:

0.202

AC XY:

15040

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.255

Gnomad4 AMR

AF:

0.223

Gnomad4 ASJ

AF:

0.201

Gnomad4 EAS

AF:

0.199

Gnomad4 SAS

AF:

0.142

Gnomad4 FIN

AF:

0.159

Gnomad4 NFE

AF:

0.182

Gnomad4 OTH

AF:

0.191

Alfa

AF:

0.188

Hom.:

4689

Bravo

AF:

0.213

TwinsUK

AF:

0.189

AC:

702

ALSPAC

AF:

0.193

AC:

745

ESP6500AA

AF:

0.246

AC:

1083

ESP6500EA

AF:

0.177

AC:

1522

ExAC

AF:

0.192

AC:

23292

Asia WGS

AF:

0.172

AC:

597

AN:

3478

EpiCase

AF:

0.180

EpiControl

AF:

0.186

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	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. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 03, 2021	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 07, 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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	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 -

Purine-nucleoside phosphorylase deficiency

Benign:5

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Oct 25, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Dec 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 2018	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. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

NUCLEOSIDE PHOSPHORYLASE POLYMORPHISM

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Oct 01, 1992

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.0050

T;T;.

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.66

T;T;T

MetaRNN

Benign

0.0010

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.2

.;N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

2.4

N;N;N

REVEL

Uncertain

0.30

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.84

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.024

MPC

0.25

ClinPred

0.0097

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.084

gMVP

0.45

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