rs2010795

Variant names:

• chr21-43752747-G-A
• rs2010795
• NM_003681.5:c.622+118G>A

Your query was ambiguous. Multiple possible variants found:

• chr21-43752747-G-A
• chr21-43752747-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.91
• Publications: 19 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 -20 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 VariationId is 1286429.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 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.622+118G>A		intron	N/A	NP_003672.1	O00764-1
	PDXK	NM_001331030.2		c.502+118G>A		intron	N/A	NP_001317959.1	F2Z2Y4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDXK	ENST00000291565.9	TSL:1 MANE Select	c.622+118G>A		intron	N/A	ENSP00000291565.4	O00764-1
	PDXK	ENST00000468090.5	TSL:1	c.538+118G>A		intron	N/A	ENSP00000418359.1	O00764-2
	PDXK	ENST00000343528.10	TSL:1	n.592+118G>A		intron	N/A

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

African (AFR) AF: 0.317 AC: 4454 AN: 14062

American (AMR) AF: 0.386 AC: 10390 AN: 26886

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 5310 AN: 15516

East Asian (EAS) AF: 0.436 AC: 13234 AN: 30332

South Asian (SAS) AF: 0.313 AC: 15830 AN: 50562

European-Finnish (FIN) AF: 0.280 AC: 8647 AN: 30904

Middle Eastern (MID) AF: 0.289 AC: 965 AN: 3344

European-Non Finnish (NFE) AF: 0.304 AC: 87598 AN: 288208

Other (OTH) AF: 0.321 AC: 8838 AN: 27520

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

African (AFR) AF: 0.321 AC: 13290 AN: 41456

American (AMR) AF: 0.377 AC: 5757 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1145 AN: 3470

East Asian (EAS) AF: 0.472 AC: 2437 AN: 5168

South Asian (SAS) AF: 0.318 AC: 1535 AN: 4820

European-Finnish (FIN) AF: 0.303 AC: 3200 AN: 10574

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.301 AC: 20458 AN: 67970

Other (OTH) AF: 0.351 AC: 741 AN: 2112

Alfa AF: 0.314 Hom.: 24121

Bravo AF: 0.334

Asia WGS AF: 0.366 AC: 1275 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.40
PhyloP100		1.9
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: rs2010795; hg19: chr21-45172628; COSMIC: COSV107339142; COSMIC: COSV107339142;