Variant 21-43746121-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003681.5(PDXK):c.374C>T(p.Ser125Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,612,004 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 17 hom. )

Consequence

PDXK
NM_003681.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.29

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014126718).

BP6

Variant 21-43746121-C-T is Benign according to our data. Variant chr21-43746121-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1013193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDXK	NM_003681.5 linkuse as main transcript	c.374C>T	p.Ser125Leu	missense_variant	5/11	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.374C>T	p.Ser125Leu	missense_variant	5/11	1	NM_003681.5	ENSP00000291565.4		O00764-1

Frequencies

GnomAD3 genomes

AF:

0.00222

AC:

338

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000604

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00384

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00218

AC:

549

AN:

251384

Hom.:

AF XY:

0.00215

AC XY:

292

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00118

Gnomad FIN exome

AF:

0.00397

Gnomad NFE exome

AF:

0.00339

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00301

AC:

4399

AN:

1459750

Hom.:

Cov.:

AF XY:

0.00297

AC XY:

2156

AN XY:

726364

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.000804

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00148

Gnomad4 FIN exome

AF:

0.00419

Gnomad4 NFE exome

AF:

0.00348

Gnomad4 OTH exome

AF:

0.00214

GnomAD4 genome

AF:

0.00221

AC:

337

AN:

152254

Hom.:

Cov.:

AF XY:

0.00201

AC XY:

150

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00311

Gnomad4 NFE

AF:

0.00384

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00302

Hom.:

Bravo

AF:

0.00182

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00349

AC:

ExAC

AF:

0.00252

AC:

306

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00354

EpiControl

AF:

0.00284

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	PDXK: BP4, BS2 -

Neuropathy, hereditary motor and sensory, type VIc, with optic atrophy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jul 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.36

.;T;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.055

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Benign

-0.51

MutationAssessor

Uncertain

2.6

.;M;.

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.8

D;D;D

REVEL

Uncertain

0.30

Sift

Benign

0.059

T;T;T

Sift4G

Benign

0.33

T;T;T

Polyphen

0.45

B;P;.

Vest4

0.48

MVP

0.69

MPC

0.56

ClinPred

0.036

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.50

gMVP

0.78

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