rs4873556

Variant names:

• chr8-51500041-G-A
• rs4873556
• NM_144651.5:c.381-271C>T

Variant summary

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

The NM_144651.5(PXDNL):​c.381-271C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,884 control chromosomes in the GnomAD database, including 8,765 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 0.32 (8765 hom., cov: 32)
• Consequence: PXDNL NM_144651.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PXDNL	NM_144651.5	c.381-271C>T		intron_variant	Intron 4 of 22	ENST00000356297.5	NP_653252.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PXDNL	ENST00000356297.5	c.381-271C>T		intron_variant	Intron 4 of 22	1	NM_144651.5	ENSP00000348645.4

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48860 AN: 151766 Hom.: 8738 Cov.: 32

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.0914

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.322 AC: 48945 AN: 151884 Hom.: 8765 Cov.: 32 AF XY: 0.324 AC XY: 24044 AN XY: 74234

African (AFR) AF: 0.469 AC: 19429 AN: 41416

American (AMR) AF: 0.311 AC: 4739 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 937 AN: 3468

East Asian (EAS) AF: 0.0914 AC: 473 AN: 5174

South Asian (SAS) AF: 0.280 AC: 1343 AN: 4798

European-Finnish (FIN) AF: 0.326 AC: 3432 AN: 10526

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17624 AN: 67936

Other (OTH) AF: 0.325 AC: 686 AN: 2112

Alfa AF: 0.306 Hom.: 1325

Bravo AF: 0.323

Asia WGS AF: 0.240 AC: 836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.39
DANN	Benign	0.51
PhyloP100		0.032
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: rs4873556; hg19: chr8-52412601;