rs2010795

chr21-43752747-G-A

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.622+118G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 639,370 control chromosomes in the GnomAD database, including 33,323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (7959 hom., cov: 32)
  • Exomes 𝑓: 0.32 (25364 hom.)
• Consequence: PDXK NM_003681.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.91

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 21-43752747-G-A is Benign according to our data. Variant chr21-43752747-G-A is described in ClinVar as [Benign]. Clinvar id is 1286429.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDXK	NM_003681.5	c.622+118G>A		intron_variant		ENST00000291565.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDXK	ENST00000291565.9	c.622+118G>A		intron_variant		1	NM_003681.5	P1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49052 AN: 151916 Hom.: 7954 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.483

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.348

GnomAD4 exome AF: 0.319 AC: 155266 AN: 487334 Hom.: 25364 AF XY: 0.317 AC XY: 81604 AN XY: 257604

Gnomad4 AFR exome AF: 0.317

Gnomad4 AMR exome AF: 0.386

Gnomad4 ASJ exome AF: 0.342

Gnomad4 EAS exome AF: 0.436

Gnomad4 SAS exome AF: 0.313

Gnomad4 FIN exome AF: 0.280

Gnomad4 NFE exome AF: 0.304

Gnomad4 OTH exome AF: 0.321

GnomAD4 genome AF: 0.323 AC: 49089 AN: 152036 Hom.: 7959 Cov.: 32 AF XY: 0.324 AC XY: 24093 AN XY: 74316

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.351

Alfa AF: 0.313 Hom.: 15119

Bravo AF: 0.334

Asia WGS AF: 0.366 AC: 1275 AN: 3478

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.9
Dann	Benign	0.40

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: rs2010795; hg19: chr21-45172628;