Genetic Variant PDXP:p.Leu16Val (chr22-37658828-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020315.5(PDXP):c.46C>G(p.Leu16Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000961 in 1,040,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

PDXP
NM_020315.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.52

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20162982).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDXP	NM_020315.5 link	c.46C>G	p.Leu16Val	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.46C>G	p.Leu16Val	missense_variant	Exon 1 of 2	1	NM_020315.5	ENSP00000215904.6		Q96GD0-1
ENSG00000285304	ENST00000451997.6 link	c.1501+4955C>G		intron_variant	Intron 16 of 16	2		ENSP00000401076.2		F8WEQ3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000961

AC:

AN:

1040432

Hom.:

Cov.:

AF XY:

0.00000814

AC XY:

AN XY:

491394

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21674

American (AMR)

AF:

0.00

AC:

AN:

6996

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12090

East Asian (EAS)

AF:

0.00

AC:

AN:

23112

South Asian (SAS)

AF:

0.00

AC:

AN:

19930

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19974

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2648

European-Non Finnish (NFE)

AF:

0.0000112

AC:

AN:

893666

Other (OTH)

AF:

0.00

AC:

AN:

40342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 13, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.46C>G (p.L16V) alteration is located in exon 1 (coding exon 1) of the PDXP gene. This alteration results from a C to G substitution at nucleotide position 46, causing the leucine (L) at amino acid position 16 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

Benign

0.16

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.032

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.28

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.52

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

2.5

PROVEAN

Benign

-1.4

REVEL

Benign

0.039

Sift

Benign

0.084

Sift4G

Benign

0.23

Polyphen

0.38

Vest4

0.23

MutPred

0.40

Gain of MoRF binding (P = 0.0846);

MVP

0.21

MPC

1.9

ClinPred

0.57

GERP RS

0.34

PromoterAI

0.071

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.41

Mutation Taster

=33/67

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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22-37658828-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over