NM_020315.5:c.668C>G

Variant names:

• chr22-37665648-C-G
• rs374362898
• NM_020315.5:c.668C>G

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.668C>G​(p.Thr223Arg) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T223M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PDXP NM_020315.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.76
• Publications: 2 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=0.14238414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDXP	NM_020315.5	c.668C>G	p.Thr223Arg	missense_variant	Exon 2 of 2	ENST00000215904.7	NP_064711.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDXP	ENST00000215904.7	c.668C>G	p.Thr223Arg	missense_variant	Exon 2 of 2	1	NM_020315.5	ENSP00000215904.6
ENSG00000285304	ENST00000451997.6	c.1595C>G	p.Thr532Arg	missense_variant	Exon 17 of 17	2		ENSP00000401076.2
PDXP	ENST00000403251.1	c.17C>G	p.Thr6Arg	missense_variant	Exon 2 of 2	2		ENSP00000385336.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.025	.;T;.
Eigen	Benign	-0.062
Eigen_PC	Benign	0.014
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.85	T;D;D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.36	.;N;.
PhyloP100		2.8
PROVEAN	Benign	-1.6	.;N;N
REVEL	Benign	0.18
Sift	Benign	0.54	.;T;T
Sift4G	Benign	0.52	.;T;T
Polyphen		0.92	.;P;.
Vest4		0.45, 0.34
MutPred		0.32		Loss of phosphorylation at T532 (P = 0.0442);.;.;
MVP		0.46
MPC		0.46
ClinPred		0.66	D
GERP RS		4.5
Varity_R		0.15
gMVP		0.79
Mutation Taster		=44/56	disease causing

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: rs374362898; hg19: chr22-38061655;