Genetic Variant NM_020315.5:c.266C>T (chr22-37659048-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_020315.5(PDXP):c.266C>T(p.Ala89Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000135 in 147,742 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PDXP
NM_020315.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.34

Publications

0 publications found

Variant links:

Genes affected

PDXP (HGNC:30259): (pyridoxal phosphatase) Pyridoxal 5-prime-phosphate (PLP) is the active form of vitamin B6 that acts as a coenzyme in maintaining biochemical homeostasis. The preferred degradation route from PLP to 4-pyridoxic acid involves the dephosphorylation of PLP by PDXP (Jang et al., 2003 [PubMed 14522954]).[supplied by OMIM, Mar 2008]

PDXP links:

ENSG00000285304 (HGNC:):

ENSG00000285304 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDXP	NM_020315.5 link	c.266C>T	p.Ala89Val	missense_variant	Exon 1 of 2	ENST00000215904.7	NP_064711.1	Q96GD0-1A0A024R1I3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDXP	ENST00000215904.7 link	c.266C>T	p.Ala89Val	missense_variant	Exon 1 of 2	1	NM_020315.5	ENSP00000215904.6		Q96GD0-1
ENSG00000285304	ENST00000451997.6 link	c.1501+5175C>T		intron_variant	Intron 16 of 16	2		ENSP00000401076.2		F8WEQ3

Frequencies

GnomAD3 genomes

AF:

0.0000135

AC:

AN:

147742

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

987762

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

464918

African (AFR)

AF:

0.00

AC:

AN:

19494

American (AMR)

AF:

0.00

AC:

AN:

5448

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10230

East Asian (EAS)

AF:

0.00

AC:

AN:

17562

South Asian (SAS)

AF:

0.00

AC:

AN:

19210

European-Finnish (FIN)

AF:

0.00

AC:

AN:

16314

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2430

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

860258

Other (OTH)

AF:

0.00

AC:

AN:

36816

GnomAD4 genome

AF:

0.0000135

AC:

AN:

147742

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71940

show subpopulations

African (AFR)

AF:

0.0000244

AC:

AN:

40922

American (AMR)

AF:

0.00

AC:

AN:

14878

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3404

East Asian (EAS)

AF:

0.00

AC:

AN:

5128

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8942

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000151

AC:

AN:

66384

Other (OTH)

AF:

0.00

AC:

AN:

2034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 17, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.266C>T (p.A89V) alteration is located in exon 1 (coding exon 1) of the PDXP gene. This alteration results from a C to T substitution at nucleotide position 266, causing the alanine (A) at amino acid position 89 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

M_CAP

Pathogenic

0.86

MetaRNN

Uncertain

0.74

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.6

PhyloP100

3.3

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.26

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.017

Polyphen

1.0

Vest4

0.41

MutPred

0.66

Loss of helix (P = 0.0444);

MVP

0.69

MPC

3.1

ClinPred

0.97

GERP RS

5.0

PromoterAI

0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.70

gMVP

0.54

Mutation Taster

=30/70

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over