rs1130650

Variant names:

• chr14-20472467-C-T
• rs1130650
• NM_000270.4:c.171C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-20472467-C-T
• chr14-20472467-C-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000270.4(PNP):​c.171C>T​(p.Pro57Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,609,224 control chromosomes in the GnomAD database, including 28,595 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3216 hom., cov: 32)
  • Exomes 𝑓: 0.18 (25379 hom.)
• Consequence: PNP NM_000270.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.723
• Publications: 39 publications found

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 Gene-Disease associations (from GenCC):

• purine nucleoside phosphorylase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 14-20472467-C-T is Benign according to our data. Variant chr14-20472467-C-T is described in ClinVar as Benign. ClinVar VariationId is 138730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.723 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000270.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNP	NM_000270.4	MANE Select	c.171C>T	p.Pro57Pro	synonymous	Exon 2 of 6	NP_000261.2	P00491

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNP	ENST00000361505.10	TSL:1 MANE Select	c.171C>T	p.Pro57Pro	synonymous	Exon 2 of 6	ENSP00000354532.6	P00491
	PNP	ENST00000556293.6	TSL:1	n.290C>T		non_coding_transcript_exon	Exon 2 of 3
	PNP	ENST00000557229.6	TSL:1	n.290C>T		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30917 AN: 152070 Hom.: 3207 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.189

GnomAD2 exomes AF: 0.191 AC: 48051 AN: 251190 AF XY: 0.187

Gnomad AFR exome AF: 0.250

Gnomad AMR exome AF: 0.235

Gnomad ASJ exome AF: 0.199

Gnomad EAS exome AF: 0.194

Gnomad FIN exome AF: 0.165

Gnomad NFE exome AF: 0.183

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.183 AC: 267158 AN: 1457036 Hom.: 25379 Cov.: 32 AF XY: 0.182 AC XY: 132006 AN XY: 725124

African (AFR) AF: 0.257 AC: 8575 AN: 33334

American (AMR) AF: 0.234 AC: 10468 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 5350 AN: 26104

East Asian (EAS) AF: 0.210 AC: 8323 AN: 39686

South Asian (SAS) AF: 0.152 AC: 13114 AN: 86162

European-Finnish (FIN) AF: 0.164 AC: 8764 AN: 53408

Middle Eastern (MID) AF: 0.207 AC: 1191 AN: 5750

European-Non Finnish (NFE) AF: 0.181 AC: 200018 AN: 1107652

Other (OTH) AF: 0.189 AC: 11355 AN: 60228

GnomAD4 genome AF: 0.203 AC: 30962 AN: 152188 Hom.: 3216 Cov.: 32 AF XY: 0.201 AC XY: 14956 AN XY: 74400

African (AFR) AF: 0.251 AC: 10414 AN: 41502

American (AMR) AF: 0.223 AC: 3406 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 697 AN: 3470

East Asian (EAS) AF: 0.200 AC: 1035 AN: 5170

South Asian (SAS) AF: 0.143 AC: 689 AN: 4834

European-Finnish (FIN) AF: 0.159 AC: 1687 AN: 10598

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12390 AN: 68002

Other (OTH) AF: 0.189 AC: 399 AN: 2112

Alfa AF: 0.191 Hom.: 8630

Bravo AF: 0.211

Asia WGS AF: 0.171 AC: 596 AN: 3478

EpiCase AF: 0.180

EpiControl AF: 0.187

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	4	Purine-nucleoside phosphorylase deficiency (4)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	4.0
DANN	Benign	0.72
PhyloP100		-0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1130650; hg19: chr14-20940626; COSMIC: COSV64091843; COSMIC: COSV64091843;