22-37659080-C-T

Variant names:

• chr22-37659080-C-T
• rs1933143784
• NM_020315.5:c.298C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_020315.5(PDXP):​c.298C>T​(p.Leu100Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000184 in 1,087,686 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000068 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: PDXP NM_020315.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=1.33 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDXP	NM_020315.5	c.298C>T	p.Leu100Leu	synonymous_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.298C>T	p.Leu100Leu	synonymous_variant	Exon 1 of 2	1	NM_020315.5	ENSP00000215904.6
ENSG00000285304	ENST00000451997.6	c.1501+5207C>T		intron_variant	Intron 16 of 16	2		ENSP00000401076.2

Frequencies

GnomAD3 genomes AF: 0.00000680 AC: 1 AN: 147130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000675

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: 0.00000106 AC: 1 AN: 940556 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 441210

African (AFR) AF: 0.00 AC: 0 AN: 18288

American (AMR) AF: 0.00 AC: 0 AN: 4150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8548

East Asian (EAS) AF: 0.00 AC: 0 AN: 12260

South Asian (SAS) AF: 0.00 AC: 0 AN: 18282

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11842

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2202

European-Non Finnish (NFE) AF: 0.00000120 AC: 1 AN: 831100

Other (OTH) AF: 0.00 AC: 0 AN: 33884

GnomAD4 genome AF: 0.00000680 AC: 1 AN: 147130 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 71596

African (AFR) AF: 0.00 AC: 0 AN: 40896

American (AMR) AF: 0.0000675 AC: 1 AN: 14822

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3390

East Asian (EAS) AF: 0.00 AC: 0 AN: 5128

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8686

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66134

Other (OTH) AF: 0.00 AC: 0 AN: 2028

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.4
DANN	Benign	0.92
PhyloP100		1.3
PromoterAI		-0.027	Neutral

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: rs1933143784; hg19: chr22-38055087;