Variant 21-43743833-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003681.5(PDXK):c.331+26T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0334 in 1,547,976 control chromosomes in the GnomAD database, including 1,006 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 90 hom., cov: 31)

Exomes 𝑓: 0.034 ( 916 hom. )

Consequence

PDXK
NM_003681.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.112

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 21-43743833-T-G is Benign according to our data. Variant chr21-43743833-T-G is described in ClinVar as [Benign]. Clinvar id is 1327004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0972 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.331+26T>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.331+26T>G		intron_variant		1	NM_003681.5	ENSP00000291565.4		O00764-1

Frequencies

GnomAD3 genomes

AF:

0.0306

AC:

4647

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0259

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.0301

Gnomad ASJ

AF:

0.0755

Gnomad EAS

AF:

0.000583

Gnomad SAS

AF:

0.0367

Gnomad FIN

AF:

0.0106

Gnomad MID

AF:

0.0962

Gnomad NFE

AF:

0.0351

Gnomad OTH

AF:

0.0339

GnomAD3 exomes

AF:

0.0315

AC:

7422

AN:

235382

Hom.:

178

AF XY:

0.0337

AC XY:

4310

AN XY:

127930

show subpopulations

Gnomad AFR exome

AF:

0.0250

Gnomad AMR exome

AF:

0.0213

Gnomad ASJ exome

AF:

0.0771

Gnomad EAS exome

AF:

0.000287

Gnomad SAS exome

AF:

0.0440

Gnomad FIN exome

AF:

0.0117

Gnomad NFE exome

AF:

0.0364

Gnomad OTH exome

AF:

0.0428

GnomAD4 exome

AF:

0.0337

AC:

47010

AN:

1395846

Hom.:

916

Cov.:

AF XY:

0.0345

AC XY:

24085

AN XY:

697482

show subpopulations

Gnomad4 AFR exome

AF:

0.0259

Gnomad4 AMR exome

AF:

0.0220

Gnomad4 ASJ exome

AF:

0.0775

Gnomad4 EAS exome

AF:

0.000128

Gnomad4 SAS exome

AF:

0.0434

Gnomad4 FIN exome

AF:

0.0127

Gnomad4 NFE exome

AF:

0.0341

Gnomad4 OTH exome

AF:

0.0411

GnomAD4 genome

AF:

0.0305

AC:

4646

AN:

152130

Hom.:

Cov.:

AF XY:

0.0292

AC XY:

2171

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0260

Gnomad4 AMR

AF:

0.0301

Gnomad4 ASJ

AF:

0.0755

Gnomad4 EAS

AF:

0.000584

Gnomad4 SAS

AF:

0.0364

Gnomad4 FIN

AF:

0.0106

Gnomad4 NFE

AF:

0.0351

Gnomad4 OTH

AF:

0.0336

Alfa

AF:

0.0391

Hom.:

Bravo

AF:

0.0320

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.7

DANN

Benign

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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