rs139180868

Variant names:

• chr21-43737181-C-T
• rs139180868
• ENST00000621478.1:c.34C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000621478.1(PDXK):​c.34C>T​(p.Arg12Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00579 in 1,449,126 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (28 hom.)
• Consequence: PDXK ENST00000621478.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0850
• Publications: 0 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)

LOC105372824 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009555101).
• BP6: Variant 21-43737181-C-T is Benign according to our data. Variant chr21-43737181-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1176767.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 28 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000621478.1. 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+3058C>T		intron	N/A	NP_003672.1	O00764-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDXK	ENST00000621478.1	TSL:1	c.34C>T	p.Arg12Trp	missense	Exon 2 of 2	ENSP00000479315.1	A0A0B4J2C9
	PDXK	ENST00000291565.9	TSL:1 MANE Select	c.142+3058C>T		intron	N/A	ENSP00000291565.4	O00764-1
	PDXK	ENST00000468090.5	TSL:1	c.142+3058C>T		intron	N/A	ENSP00000418359.1	O00764-2

Frequencies

GnomAD3 genomes AF: 0.00351 AC: 534 AN: 152204 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00367

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00587

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.00606 AC: 7855 AN: 1296804 Hom.: 28 Cov.: 28 AF XY: 0.00588 AC XY: 3707 AN XY: 630164

African (AFR) AF: 0.000898 AC: 26 AN: 28954

American (AMR) AF: 0.000794 AC: 20 AN: 25202

Ashkenazi Jewish (ASJ) AF: 0.000801 AC: 16 AN: 19970

East Asian (EAS) AF: 0.00 AC: 0 AN: 34808

South Asian (SAS) AF: 0.00132 AC: 86 AN: 64972

European-Finnish (FIN) AF: 0.00348 AC: 106 AN: 30498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5144

European-Non Finnish (NFE) AF: 0.00708 AC: 7317 AN: 1033228

Other (OTH) AF: 0.00526 AC: 284 AN: 54028

GnomAD4 genome AF: 0.00349 AC: 532 AN: 152322 Hom.: 1 Cov.: 32 AF XY: 0.00336 AC XY: 250 AN XY: 74496

African (AFR) AF: 0.00108 AC: 45 AN: 41572

American (AMR) AF: 0.00189 AC: 29 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4824

European-Finnish (FIN) AF: 0.00367 AC: 39 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00587 AC: 399 AN: 68018

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00386 Hom.: 1

Bravo AF: 0.00312

TwinsUK AF: 0.00782 AC: 29

ALSPAC AF: 0.00804 AC: 31

ESP6500AA AF: 0.00145 AC: 2

ESP6500EA AF: 0.00534 AC: 17

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.51
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0096	T
PhyloP100		-0.085
Vest4		0.19
MVP		0.17
GERP RS		0.94
Mutation Taster		=100/0	polymorphism

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: rs139180868; hg19: chr21-45157062;