rs7837348

chr8-51483681-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_144651.5(PXDNL):c.486A>G(p.Pro162=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,510,642 control chromosomes in the GnomAD database, including 25,352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (5145 hom., cov: 33)
  • Exomes 𝑓: 0.16 (20207 hom.)
• Consequence: PXDNL NM_144651.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.48

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

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 8-51483681-T-C is Benign according to our data. Variant chr8-51483681-T-C is described in ClinVar as [Benign]. Clinvar id is 403358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.48 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PXDNL	NM_144651.5	c.486A>G	p.Pro162=	synonymous_variant	6/23	ENST00000356297.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXDNL	ENST00000356297.5	c.486A>G	p.Pro162=	synonymous_variant	6/23	1	NM_144651.5	P1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35925 AN: 152018 Hom.: 5124 Cov.: 33

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.0591

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.227

GnomAD3 exomes AF: 0.183 AC: 27691 AN: 151224 Hom.: 2899 AF XY: 0.180 AC XY: 14388 AN XY: 79840

Gnomad AFR exome AF: 0.403

Gnomad AMR exome AF: 0.216

Gnomad ASJ exome AF: 0.127

Gnomad EAS exome AF: 0.0586

Gnomad SAS exome AF: 0.198

Gnomad FIN exome AF: 0.192

Gnomad NFE exome AF: 0.164

Gnomad OTH exome AF: 0.170

GnomAD4 exome AF: 0.164 AC: 222576 AN: 1358506 Hom.: 20207 Cov.: 26 AF XY: 0.165 AC XY: 110906 AN XY: 671748

Gnomad4 AFR exome AF: 0.396

Gnomad4 AMR exome AF: 0.219

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.0594

Gnomad4 SAS exome AF: 0.202

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome AF: 0.237 AC: 36006 AN: 152136 Hom.: 5145 Cov.: 33 AF XY: 0.237 AC XY: 17655 AN XY: 74388

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.0592

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.228

Alfa AF: 0.193 Hom.: 1945

Bravo AF: 0.243

Asia WGS AF: 0.188 AC: 656 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

PXDNL-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 05, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.8
Dann	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7837348; hg19: chr8-52396241; COSMIC: COSV62496633;