rs2299806

Variant names:

• chr21-43734263-C-T
• rs2299806
• NM_003681.5:c.142+140C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• neuropathy, hereditary motor and sensory, type VIc, with optic atrophy

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003681.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDXK	NM_003681.5	MANE Select	c.142+140C>T		intron	N/A	NP_003672.1	O00764-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDXK	ENST00000291565.9	TSL:1 MANE Select	c.142+140C>T		intron	N/A	ENSP00000291565.4	O00764-1
	PDXK	ENST00000468090.5	TSL:1	c.142+140C>T		intron	N/A	ENSP00000418359.1	O00764-2
	PDXK	ENST00000621478.1	TSL:1	c.-195+140C>T		intron	N/A	ENSP00000479315.1	A0A0B4J2C9

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

African (AFR) AF: 0.317 AC: 5605 AN: 17706

American (AMR) AF: 0.287 AC: 9730 AN: 33884

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 2947 AN: 19174

East Asian (EAS) AF: 0.386 AC: 12692 AN: 32850

South Asian (SAS) AF: 0.203 AC: 12777 AN: 62820

European-Finnish (FIN) AF: 0.199 AC: 7011 AN: 35232

Middle Eastern (MID) AF: 0.167 AC: 435 AN: 2600

European-Non Finnish (NFE) AF: 0.151 AC: 58276 AN: 385698

Other (OTH) AF: 0.199 AC: 6468 AN: 32450

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

African (AFR) AF: 0.321 AC: 13243 AN: 41294

American (AMR) AF: 0.277 AC: 4218 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 550 AN: 3470

East Asian (EAS) AF: 0.429 AC: 2180 AN: 5082

South Asian (SAS) AF: 0.221 AC: 1054 AN: 4776

European-Finnish (FIN) AF: 0.206 AC: 2161 AN: 10482

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 10952 AN: 67808

Other (OTH) AF: 0.230 AC: 482 AN: 2098

Alfa AF: 0.198 Hom.: 442

Bravo AF: 0.243

Asia WGS AF: 0.327 AC: 1126 AN: 3446

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.90
DANN	Benign	0.62
PhyloP100		-0.60
PromoterAI		-0.042	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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