21-43743986-G-T

Position:

• chr21-43743986-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003681.5(PDXK):​c.331+179G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0841 in 152,272 control chromosomes in the GnomAD database, including 823 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.084 (823 hom., cov: 32)
• Consequence: PDXK NM_003681.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.26

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 21-43743986-G-T is Benign according to our data. Variant chr21-43743986-G-T is described in ClinVar as [Benign]. Clinvar id is 1281595.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDXK	NM_003681.5	c.331+179G>T		intron_variant		ENST00000291565.9	NP_003672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDXK	ENST00000291565.9	c.331+179G>T		intron_variant		1	NM_003681.5	ENSP00000291565.4

Frequencies

GnomAD3 genomes AF: 0.0841 AC: 12794 AN: 152154 Hom.: 820 Cov.: 32

Gnomad AFR AF: 0.0578

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.0827

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.0733

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.0648

Gnomad OTH AF: 0.0894

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0841 AC: 12812 AN: 152272 Hom.: 823 Cov.: 32 AF XY: 0.0896 AC XY: 6673 AN XY: 74444

Gnomad4 AFR AF: 0.0578

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.0827

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.0733

Gnomad4 NFE AF: 0.0649

Gnomad4 OTH AF: 0.0918

Alfa AF: 0.0470 Hom.: 60

Bravo AF: 0.0866

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.053
DANN	Benign	0.54

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

Other links and lift over

dbSNP: rs74373568; hg19: chr21-45163867;