22-37658846-G-C

Variant names:

• chr22-37658846-G-C
• rs780427943
• NM_020315.5:c.64G>C

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.64G>C​(p.Val22Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000568 in 1,056,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. V22D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: PDXP NM_020315.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273
• 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=0.12861288).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDXP	NM_020315.5	c.64G>C	p.Val22Leu	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.64G>C	p.Val22Leu	missense_variant	Exon 1 of 2	1	NM_020315.5	ENSP00000215904.6
ENSG00000285304	ENST00000451997.6	c.1501+4973G>C		intron_variant	Intron 16 of 16	2		ENSP00000401076.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000568 AC: 6 AN: 1056874 Hom.: 0 Cov.: 31 AF XY: 0.00000399 AC XY: 2 AN XY: 500980

African (AFR) AF: 0.00 AC: 0 AN: 22358

American (AMR) AF: 0.00 AC: 0 AN: 7908

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12360

East Asian (EAS) AF: 0.00 AC: 0 AN: 24402

South Asian (SAS) AF: 0.00 AC: 0 AN: 21942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20806

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2686

European-Non Finnish (NFE) AF: 0.00000554 AC: 5 AN: 903312

Other (OTH) AF: 0.0000243 AC: 1 AN: 41100

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.43
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.59	T
M_CAP	Pathogenic	0.35	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.095	N
PhyloP100		0.27
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.034
Sift	Benign	0.32	T
Sift4G	Benign	0.45	T
Polyphen		0.0090	B
Vest4		0.23
MutPred		0.71		Loss of MoRF binding (P = 0.1026);
MVP		0.095
MPC		1.7
ClinPred		0.075	T
GERP RS		1.9
PromoterAI		-0.026	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.15
gMVP		0.39
Mutation Taster		=60/40	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: rs780427943; hg19: chr22-38054853;