Genetic Variant PDXP:p.Glu34Lys (chr22-37658882-G-A) – 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.100G>A(p.Glu34Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000164 in 1,222,254 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E34Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 9.3e-7 ( 0 hom. )

Consequence

PDXP
NM_020315.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.95

Publications

1 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:

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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.100G>A	p.Glu34Lys	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.100G>A	p.Glu34Lys	missense_variant	Exon 1 of 2	1	NM_020315.5	ENSP00000215904.6		Q96GD0-1
ENSG00000285304	ENST00000451997.6 link	c.1501+5009G>A		intron_variant	Intron 16 of 16	2		ENSP00000401076.2		F8WEQ3

Frequencies

GnomAD3 genomes

AF:

0.00000668

AC:

AN:

149698

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000664

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

26836

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.32e-7

AC:

AN:

1072556

Hom.:

Cov.:

AF XY:

0.00000196

AC XY:

AN XY:

510444

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22702

American (AMR)

AF:

0.00

AC:

AN:

8556

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12726

East Asian (EAS)

AF:

0.00

AC:

AN:

25286

South Asian (SAS)

AF:

0.00

AC:

AN:

24176

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21470

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2736

European-Non Finnish (NFE)

AF:

0.00000110

AC:

AN:

913102

Other (OTH)

AF:

0.00

AC:

AN:

41802

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000668

AC:

AN:

149698

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72986

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41158

American (AMR)

AF:

0.0000664

AC:

AN:

15068

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3426

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:

9726

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67074

Other (OTH)

AF:

0.00

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000109

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

M_CAP

Pathogenic

0.61

MetaRNN

Uncertain

0.60

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

6.9

PROVEAN

Benign

-1.2

REVEL

Benign

0.18

Sift

Benign

0.12

Sift4G

Benign

0.14

Polyphen

0.99

Vest4

0.21

MutPred

0.51

Gain of methylation at E34 (P = 0.0166);

MVP

0.83

MPC

2.0

ClinPred

0.98

GERP RS

5.2

PromoterAI

0.048

Neutral

(source)

Varity_R

0.45

gMVP

0.54

Mutation Taster

=31/69

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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chr22-37658882-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over