rs7837348

Variant names:

• chr8-51483681-T-C
• rs7837348
• NM_144651.5:c.486A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_144651.5(PXDNL):​c.486A>G​(p.Pro162Pro) 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:3
• Conservation: PhyloP100: -2.48
• Publications: 8 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 -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 VariationId 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 rank	MANE	Protein	UniProt
PXDNL	NM_144651.5	c.486A>G	p.Pro162Pro	synonymous_variant	Exon 6 of 23	ENST00000356297.5	NP_653252.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PXDNL	ENST00000356297.5	c.486A>G	p.Pro162Pro	synonymous_variant	Exon 6 of 23	1	NM_144651.5	ENSP00000348645.4

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

GnomAD2 exomes AF: 0.183 AC: 27691 AN: 151224 AF XY: 0.180

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 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

African (AFR) AF: 0.396 AC: 11835 AN: 29882

American (AMR) AF: 0.219 AC: 7673 AN: 35028

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 3171 AN: 24952

East Asian (EAS) AF: 0.0594 AC: 2106 AN: 35480

South Asian (SAS) AF: 0.202 AC: 15574 AN: 77052

European-Finnish (FIN) AF: 0.188 AC: 9260 AN: 49170

Middle Eastern (MID) AF: 0.212 AC: 1187 AN: 5602

European-Non Finnish (NFE) AF: 0.155 AC: 161839 AN: 1044674

Other (OTH) AF: 0.175 AC: 9931 AN: 56666

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

African (AFR) AF: 0.399 AC: 16562 AN: 41484

American (AMR) AF: 0.238 AC: 3641 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 440 AN: 3472

East Asian (EAS) AF: 0.0592 AC: 307 AN: 5184

South Asian (SAS) AF: 0.202 AC: 973 AN: 4818

European-Finnish (FIN) AF: 0.193 AC: 2046 AN: 10578

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11392 AN: 67998

Other (OTH) AF: 0.228 AC: 481 AN: 2108

Alfa AF: 0.197 Hom.: 2630

Bravo AF: 0.243

Asia WGS AF: 0.188 AC: 656 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 disorder Benign:1

Nov 05, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
DANN	Benign	0.44
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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