21-43733870-A-G

Position:

• chr21-43733870-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003681.5(PDXK):​c.88-199A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,188 control chromosomes in the GnomAD database, including 7,005 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.27 (7005 hom., cov: 33)
• Consequence: PDXK NM_003681.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.594

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 21-43733870-A-G is Benign according to our data. Variant chr21-43733870-A-G is described in ClinVar as [Benign]. Clinvar id is 1285764.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDXK	NM_003681.5	c.88-199A>G		intron_variant		ENST00000291565.9	NP_003672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDXK	ENST00000291565.9	c.88-199A>G		intron_variant		1	NM_003681.5	ENSP00000291565.4

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41525 AN: 152070 Hom.: 6971 Cov.: 33

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.273 AC: 41620 AN: 152188 Hom.: 7005 Cov.: 33 AF XY: 0.276 AC XY: 20502 AN XY: 74394

Gnomad4 AFR AF: 0.460

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.260

Alfa AF: 0.184 Hom.: 3543

Bravo AF: 0.289

Asia WGS AF: 0.347 AC: 1207 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.45

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: rs13050307; hg19: chr21-45153751;