rs4873584

Variant names:

• chr8-51727184-T-G
• rs4873584
• NM_144651.5:c.165-72424A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144651.5(PXDNL):​c.165-72424A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 152,172 control chromosomes in the GnomAD database, including 43,068 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.75 (43068 hom., cov: 33)
• Consequence: PXDNL NM_144651.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290
• Publications: 2 publications found

Genes affected

PXDNL (HGNC:26359): (peroxidasin like) Predicted to enable heme binding activity and peroxidase activity. Predicted to be involved in hydrogen peroxide catabolic process. Predicted to be located in cytoplasm. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PXDNL	NM_144651.5	c.165-72424A>C		intron_variant	Intron 1 of 22	ENST00000356297.5	NP_653252.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PXDNL	ENST00000356297.5	c.165-72424A>C		intron_variant	Intron 1 of 22	1	NM_144651.5	ENSP00000348645.4

Frequencies

GnomAD3 genomes AF: 0.750 AC: 114084 AN: 152054 Hom.: 43069 Cov.: 33

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.807

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.761

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.750 AC: 114136 AN: 152172 Hom.: 43068 Cov.: 33 AF XY: 0.749 AC XY: 55701 AN XY: 74406

African (AFR) AF: 0.685 AC: 28435 AN: 41498

American (AMR) AF: 0.791 AC: 12101 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.807 AC: 2797 AN: 3466

East Asian (EAS) AF: 0.862 AC: 4458 AN: 5172

South Asian (SAS) AF: 0.809 AC: 3909 AN: 4830

European-Finnish (FIN) AF: 0.732 AC: 7752 AN: 10592

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 52067 AN: 67998

Other (OTH) AF: 0.758 AC: 1603 AN: 2114

Alfa AF: 0.765 Hom.: 24523

Bravo AF: 0.754

Asia WGS AF: 0.776 AC: 2701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.52
PhyloP100		-0.029
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: rs4873584; hg19: chr8-52639744;