Variant 21-43741551-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 8P and 16B. PVS1BP6_Very_StrongBA1

The NM_001331030.2(PDXK):c.1A>G(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00728 in 1,524,412 control chromosomes in the GnomAD database, including 772 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 416 hom., cov: 31)

Exomes 𝑓: 0.0038 ( 356 hom. )

Consequence

PDXK
NM_001331030.2 start_lost

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.793

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 Benign. Variant got -8 ACMG points.

PVS1

Start lost variant, no new inframe start found.

BP6

Variant 21-43741551-A-G is Benign according to our data. Variant chr21-43741551-A-G is described in ClinVar as [Benign]. Clinvar id is 1231720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDXK	NM_003681.5 linkuse as main transcript	c.143-116A>G		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.143-116A>G		intron_variant		1	NM_003681.5	ENSP00000291565.4		O00764-1

Frequencies

GnomAD3 genomes

AF:

0.0384

AC:

5818

AN:

151442

Hom.:

414

Cov.:

show subpopulations

Gnomad AFR

AF:

0.135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0121

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000619

Gnomad OTH

AF:

0.0235

GnomAD3 exomes

AF:

0.0110

AC:

1701

AN:

155288

Hom.:

111

AF XY:

0.00827

AC XY:

685

AN XY:

82780

show subpopulations

Gnomad AFR exome

AF:

0.137

Gnomad AMR exome

AF:

0.00545

Gnomad ASJ exome

AF:

0.000208

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000504

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000530

Gnomad OTH exome

AF:

0.00457

GnomAD4 exome

AF:

0.00384

AC:

5275

AN:

1372858

Hom.:

356

Cov.:

AF XY:

0.00343

AC XY:

2315

AN XY:

675864

show subpopulations

Gnomad4 AFR exome

AF:

0.139

Gnomad4 AMR exome

AF:

0.00609

Gnomad4 ASJ exome

AF:

0.0000465

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000474

Gnomad4 FIN exome

AF:

0.0000412

Gnomad4 NFE exome

AF:

0.000234

Gnomad4 OTH exome

AF:

0.00963

GnomAD4 genome

AF:

0.0385

AC:

5828

AN:

151554

Hom.:

416

Cov.:

AF XY:

0.0373

AC XY:

2763

AN XY:

74106

show subpopulations

Gnomad4 AFR

AF:

0.135

Gnomad4 AMR

AF:

0.0120

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000619

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.0280

Hom.:

Bravo

AF:

0.0435

ESP6500AA

AF:

0.120

AC:

208

ESP6500EA

AF:

0.000758

AC:

ExAC

AF:

0.0112

AC:

1344

Asia WGS

AF:

0.00722

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -

PDXK-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 07, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.40

CADD

Benign

0.27

DANN

Benign

0.28

DEOGEN2

Benign

0.0071

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.030

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.0

PROVEAN

Benign

2.5

REVEL

Benign

0.051

Sift

Pathogenic

0.0

Vest4

0.041

ClinPred

0.025

GERP RS

-4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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