21-43743885-G-A

Position:

• chr21-43743885-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.331+78G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0047 in 946,854 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (66 hom., cov: 31)
  • Exomes 𝑓: 0.0023 (35 hom.)
• Consequence: PDXK NM_003681.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.513

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=-0.86).
• BP6: Variant 21-43743885-G-A is Benign according to our data. Variant chr21-43743885-G-A is described in ClinVar as [Benign]. Clinvar id is 1243627.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDXK	NM_003681.5	c.331+78G>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.331+78G>A		intron_variant		1	NM_003681.5	ENSP00000291565.4

Frequencies

GnomAD3 genomes AF: 0.0172 AC: 2621 AN: 152092 Hom.: 67 Cov.: 31

Gnomad AFR AF: 0.0585

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00831

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0138

GnomAD4 exome AF: 0.00230 AC: 1829 AN: 794644 Hom.: 35 AF XY: 0.00187 AC XY: 778 AN XY: 415864

Gnomad4 AFR exome AF: 0.0575

Gnomad4 AMR exome AF: 0.00595

Gnomad4 ASJ exome AF: 0.00169

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000381

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000277

Gnomad4 OTH exome AF: 0.00603

GnomAD4 genome AF: 0.0172 AC: 2624 AN: 152210 Hom.: 66 Cov.: 31 AF XY: 0.0161 AC XY: 1197 AN XY: 74416

Gnomad4 AFR AF: 0.0585

Gnomad4 AMR AF: 0.00830

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.000285 Hom.: 0

Bravo AF: 0.0200

Asia WGS AF: 0.00635 AC: 23 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	clinical testing	GeneDx	May 14, 2021	- -
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	-0.86
CADD	Benign	0.97
DANN	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs73375218; hg19: chr21-45163766;