22-37658876-A-G

Variant names:

• chr22-37658876-A-G
• rs779069897
• NM_020315.5:c.94A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020315.5(PDXP):​c.94A>G​(p.Asn32Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000271 in 1,219,954 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: 𝑓 0.00010 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (0 hom.)
• Consequence: PDXP NM_020315.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.866
• Publications: 0 publications found

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]

ENSG00000285304 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06597182).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDXP	NM_020315.5	c.94A>G	p.Asn32Asp	missense_variant	Exon 1 of 2	ENST00000215904.7	NP_064711.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDXP	ENST00000215904.7	c.94A>G	p.Asn32Asp	missense_variant	Exon 1 of 2	1	NM_020315.5	ENSP00000215904.6
ENSG00000285304	ENST00000451997.6	c.1501+5003A>G		intron_variant	Intron 16 of 16	2		ENSP00000401076.2

Frequencies

GnomAD3 genomes AF: 0.000101 AC: 15 AN: 148432 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000246

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: 0.000210

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000695 AC: 2 AN: 28778 AF XY: 0.0000620

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: 0.000109

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000295 AC: 316 AN: 1071522 Hom.: 0 Cov.: 31 AF XY: 0.000282 AC XY: 144 AN XY: 509864

African (AFR) AF: 0.00 AC: 0 AN: 22688

American (AMR) AF: 0.00 AC: 0 AN: 8584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12676

East Asian (EAS) AF: 0.00 AC: 0 AN: 25250

South Asian (SAS) AF: 0.00 AC: 0 AN: 24022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2724

European-Non Finnish (NFE) AF: 0.000311 AC: 284 AN: 912438

Other (OTH) AF: 0.000767 AC: 32 AN: 41696

GnomAD4 genome AF: 0.000101 AC: 15 AN: 148432 Hom.: 0 Cov.: 32 AF XY: 0.0000691 AC XY: 5 AN XY: 72310

African (AFR) AF: 0.0000246 AC: 1 AN: 40694

American (AMR) AF: 0.00 AC: 0 AN: 14992

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3416

East Asian (EAS) AF: 0.00 AC: 0 AN: 5078

South Asian (SAS) AF: 0.00 AC: 0 AN: 4766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.000210 AC: 14 AN: 66644

Other (OTH) AF: 0.00 AC: 0 AN: 2048

Alfa AF: 0.000427 Hom.: 0

Bravo AF: 0.000136

ExAC AF: 0.0000431 AC: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.94A>G (p.N32D) alteration is located in exon 1 (coding exon 1) of the PDXP gene. This alteration results from a A to G substitution at nucleotide position 94, causing the asparagine (N) at amino acid position 32 to be replaced by an aspartic acid (D). 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	0.21
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.65	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.24	N
PhyloP100		0.87
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.045
Sift	Benign	0.32	T
Sift4G	Benign	0.54	T
Polyphen		0.13	B
Vest4		0.14
MutPred		0.53		Loss of helix (P = 0.079);
MVP		0.28
MPC		2.0
ClinPred		0.081	T
GERP RS		4.1
PromoterAI		0.015	Neutral
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.8
Varity_R		0.35
gMVP		0.39
Mutation Taster		=54/46	polymorphism

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

Other links and lift over

dbSNP: rs779069897; hg19: chr22-38054883;