14-20472312-A-G

Position:

• chr14-20472312-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000270.4(PNP):​c.16A>G​(p.Thr6Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PNP NM_000270.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.35

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28218913).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNP	NM_000270.4	c.16A>G	p.Thr6Ala	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	c.16A>G	p.Thr6Ala	missense_variant	2/6	1	NM_000270.4	ENSP00000354532.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461128 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726918

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.036	T;T;.
Eigen	Benign	-0.095
Eigen_PC	Benign	0.021
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.63	T;T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Uncertain	0.64	D
MutationAssessor	Uncertain	2.0	.;M;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.21
Sift	Benign	0.091	T;T;D
Sift4G	Benign	0.16	T;T;T
Polyphen		0.13	B;B;.
Vest4		0.21
MutPred		0.17		Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);.;
MVP		0.93
MPC		0.25
ClinPred		0.45	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.29
gMVP		0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-20940471;