rs10755971

Variant names:

• chr8-51502860-T-C
• rs10755971
• NM_144651.5:c.381-3090A>G

Variant summary

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

The NM_144651.5(PXDNL):​c.381-3090A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,970 control chromosomes in the GnomAD database, including 18,431 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 0.47 (18431 hom., cov: 31)
• Consequence: PXDNL NM_144651.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 4 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PXDNL	NM_144651.5	c.381-3090A>G		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.381-3090A>G		intron_variant	Intron 4 of 22	1	NM_144651.5	ENSP00000348645.4

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71706 AN: 151852 Hom.: 18378 Cov.: 31

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.473 AC: 71827 AN: 151970 Hom.: 18431 Cov.: 31 AF XY: 0.476 AC XY: 35323 AN XY: 74250

African (AFR) AF: 0.685 AC: 28394 AN: 41434

American (AMR) AF: 0.430 AC: 6556 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1438 AN: 3470

East Asian (EAS) AF: 0.368 AC: 1895 AN: 5154

South Asian (SAS) AF: 0.474 AC: 2284 AN: 4814

European-Finnish (FIN) AF: 0.435 AC: 4589 AN: 10548

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.370 AC: 25158 AN: 67972

Other (OTH) AF: 0.478 AC: 1009 AN: 2112

Alfa AF: 0.400 Hom.: 31964

Bravo AF: 0.477

Asia WGS AF: 0.493 AC: 1715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.18
DANN	Benign	0.36
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs10755971; hg19: chr8-52415420;