8-51510272-C-T

Variant names:

• chr8-51510272-C-T
• rs10504121
• NM_144651.5:c.381-10502G>A

Variant summary

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

The NM_144651.5(PXDNL):​c.381-10502G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 151,936 control chromosomes in the GnomAD database, including 11,283 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 0.37 (11283 hom., cov: 30)
• Consequence: PXDNL NM_144651.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.829
• Publications: 5 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PXDNL	NM_144651.5	c.381-10502G>A		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.381-10502G>A		intron_variant	Intron 4 of 22	1	NM_144651.5	ENSP00000348645.4

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55486 AN: 151818 Hom.: 11250 Cov.: 30

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.366 AC: 55584 AN: 151936 Hom.: 11283 Cov.: 30 AF XY: 0.368 AC XY: 27365 AN XY: 74262

African (AFR) AF: 0.544 AC: 22537 AN: 41434

American (AMR) AF: 0.346 AC: 5291 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1054 AN: 3472

East Asian (EAS) AF: 0.339 AC: 1744 AN: 5152

South Asian (SAS) AF: 0.313 AC: 1507 AN: 4808

European-Finnish (FIN) AF: 0.342 AC: 3607 AN: 10534

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18762 AN: 67948

Other (OTH) AF: 0.368 AC: 777 AN: 2110

Alfa AF: 0.280 Hom.: 3463

Bravo AF: 0.370

Asia WGS AF: 0.402 AC: 1397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.48
DANN	Benign	0.61
PhyloP100		-0.83
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: rs10504121; hg19: chr8-52422832;