Variant 21-43734121-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3

The NM_003681.5(PDXK):c.140C>T(p.Thr47Ile) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000137 in 1,461,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T47T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PDXK
NM_003681.5 missense, splice_region

Scores

Splicing: ADA: 0.9261

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.25

Variant links:

Genes affected

PDXK (HGNC:8819): (pyridoxal kinase) The protein encoded by this gene phosphorylates vitamin B6, a step required for the conversion of vitamin B6 to pyridoxal-5-phosphate, an important cofactor in intermediary metabolism. The encoded protein is cytoplasmic and probably acts as a homodimer. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

PDXK links:

PDXK (HGNC:):

PDXK links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity PDXK_HUMAN

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.792

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDXK	NM_003681.5 linkuse as main transcript	c.140C>T	p.Thr47Ile	missense_variant, splice_region_variant	2/11	ENST00000291565.9	NP_003672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDXK	ENST00000291565.9 linkuse as main transcript	c.140C>T	p.Thr47Ile	missense_variant, splice_region_variant	2/11	1	NM_003681.5	ENSP00000291565.4		O00764-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461586

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2024

The c.140C>T (p.T47I) alteration is located in exon 2 (coding exon 2) of the PDXK gene. This alteration results from a C to T substitution at nucleotide position 140, causing the threonine (T) at amino acid position 47 to be replaced by an isoleucine (I). 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

Pathogenic

0.87

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.29

CADD

Pathogenic

DANN

Benign

0.96

DEOGEN2

Uncertain

0.53

.;.;D;.

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.77

T;D;D;T

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.78

D;D;D;D

MetaSVM

Uncertain

0.73

MutationAssessor

Pathogenic

3.9

.;H;H;.

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-4.8

D;D;D;D

REVEL

Pathogenic

0.87

Sift

Pathogenic

0.0

D;D;D;.

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

0.99, 0.97, 1.0

.;D;D;D

Vest4

0.61

MutPred

0.65

Loss of disorder (P = 0.0819);Loss of disorder (P = 0.0819);Loss of disorder (P = 0.0819);.;

MVP

0.94

MPC

1.6

ClinPred

1.0

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

3.7

Varity_R

0.87

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.93

dbscSNV1_RF

Benign

0.47

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over