21-43719132-A-G

Position:

• chr21-43719132-A-G

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.-163A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 297,490 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (89 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (4 hom.)
• Consequence: PDXK NM_003681.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.79

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=-0.79).
• BP6: Variant 21-43719132-A-G is Benign according to our data. Variant chr21-43719132-A-G is described in ClinVar as [Benign]. Clinvar id is 1248473.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDXK	NM_003681.5	c.-163A>G		5_prime_UTR_variant	1/11	ENST00000291565.9	NP_003672.1
PDXK	XM_047441005.1	c.-3319A>G		5_prime_UTR_variant	1/12		XP_047296961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDXK	ENST00000291565.9	c.-163A>G		5_prime_UTR_variant	1/11	1	NM_003681.5	ENSP00000291565.4

Frequencies

GnomAD3 genomes AF: 0.0195 AC: 2948 AN: 150828 Hom.: 89 Cov.: 33

Gnomad AFR AF: 0.0661

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000222

Gnomad OTH AF: 0.0154

GnomAD4 exome AF: 0.00206 AC: 302 AN: 146556 Hom.: 4 Cov.: 3 AF XY: 0.00195 AC XY: 148 AN XY: 75790

Gnomad4 AFR exome AF: 0.0557

Gnomad4 AMR exome AF: 0.00525

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000259

Gnomad4 OTH exome AF: 0.00593

GnomAD4 genome AF: 0.0195 AC: 2950 AN: 150934 Hom.: 89 Cov.: 33 AF XY: 0.0195 AC XY: 1439 AN XY: 73758

Gnomad4 AFR AF: 0.0660

Gnomad4 AMR AF: 0.0116

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000222

Gnomad4 OTH AF: 0.0153

Alfa AF: 0.0147 Hom.: 4

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 22, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	17
DANN	Benign	0.84

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: rs527362783; hg19: chr21-45139013;