NM_020315.5:c.317C>T

Variant names:

• chr22-37659099-C-T
• NM_020315.5:c.317C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020315.5(PDXP):​c.317C>T​(p.Ala106Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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)
• Consequence: PDXP NM_020315.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39
• 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: 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=0.08460942).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDXP	NM_020315.5	c.317C>T	p.Ala106Val	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.317C>T	p.Ala106Val	missense_variant	Exon 1 of 2	1	NM_020315.5	ENSP00000215904.6
ENSG00000285304	ENST00000451997.6	c.1501+5226C>T		intron_variant	Intron 16 of 16	2		ENSP00000401076.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 18, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.317C>T (p.A106V) 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 317, causing the alanine (A) at amino acid position 106 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	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.0082	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.51	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.4
PROVEAN	Benign	0.18	N
REVEL	Benign	0.042
Sift	Benign	0.59	T
Sift4G	Benign	0.67	T
Polyphen		0.031	B
Vest4		0.042
MutPred		0.37		Loss of glycosylation at P104 (P = 0.0884);
MVP		0.42
MPC		1.7
ClinPred		0.086	T
GERP RS		4.0
PromoterAI		0.056	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.095
gMVP		0.43
Mutation Taster		=72/28	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

hg19: chr22-38055106;