21-43741465-G-A

Position:

• chr21-43741465-G-A

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.143-202G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (549 hom., cov: 19)
  • Exomes 𝑓: 0.0028 (697 hom.)
• Consequence: PDXK NM_003681.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.822

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=-0.97).
• BP6: Variant 21-43741465-G-A is Benign according to our data. Variant chr21-43741465-G-A is described in ClinVar as [Benign]. Clinvar id is 1181584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDXK	NM_003681.5	c.143-202G>A		intron_variant		ENST00000291565.9	NP_003672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDXK	ENST00000291565.9	c.143-202G>A		intron_variant		1	NM_003681.5	ENSP00000291565.4

Frequencies

GnomAD3 genomes AF: 0.0287 AC: 3251 AN: 113130 Hom.: 547 Cov.: 19

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.000953

Gnomad EAS AF: 0.000655

Gnomad SAS AF: 0.000762

Gnomad FIN AF: 0.000115

Gnomad MID AF: 0.0167

Gnomad NFE AF: 0.00123

Gnomad OTH AF: 0.0299

GnomAD4 exome AF: 0.00279 AC: 2727 AN: 975832 Hom.: 697 Cov.: 14 AF XY: 0.00244 AC XY: 1138 AN XY: 466208

Gnomad4 AFR exome AF: 0.235

Gnomad4 AMR exome AF: 0.00767

Gnomad4 ASJ exome AF: 0.0000712

Gnomad4 EAS exome AF: 0.000156

Gnomad4 SAS exome AF: 0.000120

Gnomad4 FIN exome AF: 0.000104

Gnomad4 NFE exome AF: 0.000608

Gnomad4 OTH exome AF: 0.00687

GnomAD4 genome AF: 0.0288 AC: 3258 AN: 113158 Hom.: 549 Cov.: 19 AF XY: 0.0280 AC XY: 1555 AN XY: 55492

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.0122

Gnomad4 ASJ AF: 0.000953

Gnomad4 EAS AF: 0.000657

Gnomad4 SAS AF: 0.000509

Gnomad4 FIN AF: 0.000115

Gnomad4 NFE AF: 0.00123

Gnomad4 OTH AF: 0.0294

Alfa AF: 0.0750 Hom.: 69

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 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs76459079; hg19: chr21-45161346;