21-43734263-C-T

Position:

• chr21-43734263-C-T

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.142+140C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 773,842 control chromosomes in the GnomAD database, including 17,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4516 hom., cov: 31)
  • Exomes 𝑓: 0.19 (13106 hom.)
• Consequence: PDXK NM_003681.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.599

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 21-43734263-C-T is Benign according to our data. Variant chr21-43734263-C-T is described in ClinVar as [Benign]. Clinvar id is 1248707.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDXK	NM_003681.5	c.142+140C>T		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+140C>T		intron_variant		1	NM_003681.5	ENSP00000291565.4

Frequencies

GnomAD3 genomes AF: 0.231 AC: 34998 AN: 151310 Hom.: 4501 Cov.: 31

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.186 AC: 115941 AN: 622414 Hom.: 13106 AF XY: 0.186 AC XY: 61523 AN XY: 331524

Gnomad4 AFR exome AF: 0.317

Gnomad4 AMR exome AF: 0.287

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.386

Gnomad4 SAS exome AF: 0.203

Gnomad4 FIN exome AF: 0.199

Gnomad4 NFE exome AF: 0.151

Gnomad4 OTH exome AF: 0.199

GnomAD4 genome AF: 0.232 AC: 35056 AN: 151428 Hom.: 4516 Cov.: 31 AF XY: 0.235 AC XY: 17386 AN XY: 73968

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.230

Alfa AF: 0.198 Hom.: 442

Bravo AF: 0.243

Asia WGS AF: 0.327 AC: 1126 AN: 3446

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 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.90
DANN	Benign	0.62
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3

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: rs2299806; hg19: chr21-45154144; COSMIC: COSV52363510; COSMIC: COSV52363510;