rs763310083

Variant names:

• chr14-20469550-AGGCCCGCAG-A
• rs763310083
• NM_000270.4:c.11+17_11+25delGCCCGCAGG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_000270.4(PNP):​c.11+17_11+25delGCCCGCAGG variant causes a intron change. The variant allele was found at a frequency of 0.00000998 in 1,402,602 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: PNP NM_000270.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.09
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 14-20469550-AGGCCCGCAG-A is Benign according to our data. Variant chr14-20469550-AGGCCCGCAG-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2776066.Status of the report is criteria_provided_single_submitter, 1 stars.

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.11+17_11+25delGCCCGCAGG		intron	N/A	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.11+17_11+25delGCCCGCAGG		intron	N/A	ENSP00000354532.6	P00491
	PNP	ENST00000556293.6	TSL:1	n.130+17_130+25delGCCCGCAGG		intron	N/A
	PNP	ENST00000557229.6	TSL:1	n.130+17_130+25delGCCCGCAGG		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000629 AC: 1 AN: 158972 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000163

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000998 AC: 14 AN: 1402602 Hom.: 0 AF XY: 0.00000867 AC XY: 6 AN XY: 692202

African (AFR) AF: 0.00 AC: 0 AN: 31656

American (AMR) AF: 0.00 AC: 0 AN: 35910

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25224

East Asian (EAS) AF: 0.00 AC: 0 AN: 35912

South Asian (SAS) AF: 0.00 AC: 0 AN: 79400

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49640

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5364

European-Non Finnish (NFE) AF: 0.0000120 AC: 13 AN: 1081276

Other (OTH) AF: 0.0000172 AC: 1 AN: 58220

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Purine-nucleoside phosphorylase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs763310083; hg19: chr14-20937709;