Genetic Variant PDXP:p.Arg97Cys (chr22-37659071-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_020315.5(PDXP):c.289C>T(p.Arg97Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000181 in 1,107,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000010 ( 0 hom. )

Consequence

PDXP
NM_020315.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.208

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30465138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDXP	NM_020315.5 link	c.289C>T	p.Arg97Cys	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.289C>T	p.Arg97Cys	missense_variant	Exon 1 of 2	1	NM_020315.5	ENSP00000215904.6		Q96GD0-1
ENSG00000285304	ENST00000451997.6 link	c.1501+5198C>T		intron_variant	Intron 16 of 16	2		ENSP00000401076.2		F8WEQ3

Frequencies

GnomAD3 genomes

AF:

0.00000679

AC:

AN:

147340

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000104

AC:

AN:

960472

Hom.:

Cov.:

AF XY:

0.00000222

AC XY:

AN XY:

451166

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18762

American (AMR)

AF:

0.00

AC:

AN:

4672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9216

East Asian (EAS)

AF:

0.00

AC:

AN:

14666

South Asian (SAS)

AF:

0.00

AC:

AN:

18468

European-Finnish (FIN)

AF:

0.00

AC:

AN:

13850

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2296

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

843400

Other (OTH)

AF:

0.0000285

AC:

AN:

35142

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000679

AC:

AN:

147340

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71708

show subpopulations

African (AFR)

AF:

0.0000244

AC:

AN:

40906

American (AMR)

AF:

0.00

AC:

AN:

14846

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3388

East Asian (EAS)

AF:

0.00

AC:

AN:

5118

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8760

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66252

Other (OTH)

AF:

0.00

AC:

AN:

2030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 14, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.289C>T (p.R97C) 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 289, causing the arginine (R) at amino acid position 97 to be replaced by a cysteine (C). 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

0.25

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.070

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.81

M_CAP

Pathogenic

0.70

MetaRNN

Benign

0.30

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PhyloP100

-0.21

PROVEAN

Uncertain

-4.2

REVEL

Benign

0.093

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

0.0080

Vest4

0.11

MutPred

0.59

Loss of disorder (P = 0.0379);

MVP

0.41

MPC

2.2

ClinPred

0.99

GERP RS

2.9

PromoterAI

-0.045

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.53

gMVP

0.66

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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22-37659071-C-T

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