Variant 21-43737181-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000621478.1(PDXK):c.34C>T(p.Arg12Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00579 in 1,449,126 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 28 hom. )

Consequence

PDXK
ENST00000621478.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0850

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:

LOC105372824 (HGNC:):

LOC105372824 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009555101).

BP6

Variant 21-43737181-C-T is Benign according to our data. Variant chr21-43737181-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1176767.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDXK	NM_003681.5 linkuse as main transcript	c.142+3058C>T		intron_variant		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.142+3058C>T		intron_variant		1	NM_003681.5	ENSP00000291565.4		O00764-1

Frequencies

GnomAD3 genomes

AF:

0.00351

AC:

534

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00367

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00587

Gnomad OTH

AF:

0.00239

GnomAD4 exome

AF:

0.00606

AC:

7855

AN:

1296804

Hom.:

Cov.:

AF XY:

0.00588

AC XY:

3707

AN XY:

630164

show subpopulations

Gnomad4 AFR exome

AF:

0.000898

Gnomad4 AMR exome

AF:

0.000794

Gnomad4 ASJ exome

AF:

0.000801

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00132

Gnomad4 FIN exome

AF:

0.00348

Gnomad4 NFE exome

AF:

0.00708

Gnomad4 OTH exome

AF:

0.00526

GnomAD4 genome

AF:

0.00349

AC:

532

AN:

152322

Hom.:

Cov.:

AF XY:

0.00336

AC XY:

250

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.00189

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00367

Gnomad4 NFE

AF:

0.00587

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00386

Hom.:

Bravo

AF:

0.00312

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.00145

AC:

ESP6500EA

AF:

0.00534

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

PDXK: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.1

DANN

Benign

0.51

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.48

MetaRNN

Benign

0.0096

Vest4

0.19

MVP

0.17

GERP RS

0.94

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over