21-43734293-CAG-C

Position:

• chr21-43734293-CAG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003681.5(PDXK):​c.142+171_142+172delAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 151,468 control chromosomes in the GnomAD database, including 2,029 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (2029 hom., cov: 29)
• Consequence: PDXK NM_003681.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.229

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 -10 ACMG points.

• BP6: Variant 21-43734293-CAG-C is Benign according to our data. Variant chr21-43734293-CAG-C is described in ClinVar as [Benign]. Clinvar id is 1279509.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDXK	NM_003681.5	c.142+171_142+172delAG		intron_variant		ENST00000291565.9	NP_003672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDXK	ENST00000291565.9	c.142+171_142+172delAG		intron_variant		1	NM_003681.5	ENSP00000291565.4

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22121 AN: 151346 Hom.: 2027 Cov.: 29

Gnomad AFR AF: 0.0793

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.146 AC: 22138 AN: 151468 Hom.: 2029 Cov.: 29 AF XY: 0.152 AC XY: 11221 AN XY: 73970

Gnomad4 AFR AF: 0.0791

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.154

Alfa AF: 0.139 Hom.: 205

Bravo AF: 0.150

Asia WGS AF: 0.291 AC: 991 AN: 3412

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 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs3216365; hg19: chr21-45154174;