Genetic Variant PDXP:c.575-712G>A (chr22-37664843-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020315.5(PDXP):c.575-712G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 152,430 control chromosomes in the GnomAD database, including 17,438 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.47 ( 17392 hom., cov: 31)

Exomes 𝑓: 0.35 ( 46 hom. )

Consequence

PDXP
NM_020315.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.23

Publications

10 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020315.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDXP	NM_020315.5	MANE Select	c.575-712G>A		intron	N/A	NP_064711.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PDXP	ENST00000215904.7	TSL:1 MANE Select	c.575-712G>A	intron	N/A	ENSP00000215904.6
ENSG00000285304	ENST00000451997.6	TSL:2	c.1502-712G>A	intron	N/A	ENSP00000401076.2
PDXP	ENST00000403251.1	TSL:2	c.-338G>A	upstream_gene	N/A	ENSP00000385336.1

Frequencies

GnomAD3 genomes

AF:

0.473

AC:

71778

AN:

151722

Hom.:

17390

Cov.:

show subpopulations

Gnomad AFR

AF:

0.589

Gnomad AMI

AF:

0.513

Gnomad AMR

AF:

0.442

Gnomad ASJ

AF:

0.541

Gnomad EAS

AF:

0.474

Gnomad SAS

AF:

0.432

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.423

Gnomad OTH

AF:

0.474

GnomAD4 exome

AF:

0.346

AC:

204

AN:

590

Hom.:

AF XY:

0.326

AC XY:

AN XY:

298

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.266

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.361

AC:

177

AN:

490

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.473

AC:

71816

AN:

151840

Hom.:

17392

Cov.:

AF XY:

0.470

AC XY:

34857

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.589

AC:

24362

AN:

41386

American (AMR)

AF:

0.441

AC:

6734

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.541

AC:

1877

AN:

3470

East Asian (EAS)

AF:

0.473

AC:

2440

AN:

5154

South Asian (SAS)

AF:

0.432

AC:

2070

AN:

4796

European-Finnish (FIN)

AF:

0.378

AC:

3989

AN:

10546

Middle Eastern (MID)

AF:

0.476

AC:

139

AN:

292

European-Non Finnish (NFE)

AF:

0.423

AC:

28750

AN:

67930

Other (OTH)

AF:

0.470

AC:

988

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1891

3782

5674

7565

9456

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

648

1296

1944

2592

3240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.431

Hom.:

12775

Bravo

AF:

0.483

Asia WGS

AF:

0.474

AC:

1647

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.85

(source)

DANN

Benign

0.63

PhyloP100

-1.2

PromoterAI

0.057

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over