rs6473599

Variant names:

• chr8-51453640-G-A
• rs6473599
• NM_144651.5:c.1128C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-51453640-G-A
• chr8-51453640-G-T

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.1128C>T​(p.His376His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 1,613,778 control chromosomes in the GnomAD database, including 676,821 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (52908 hom., cov: 32)
  • Exomes 𝑓: 0.92 (623913 hom.)
• Consequence: PXDNL NM_144651.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.79
• Publications: 13 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=-0.72).
• BP6: Variant 8-51453640-G-A is Benign according to our data. Variant chr8-51453640-G-A is described in ClinVar as Benign. ClinVar VariationId is 403357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.79 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PXDNL	NM_144651.5	c.1128C>T	p.His376His	synonymous_variant	Exon 10 of 23	ENST00000356297.5	NP_653252.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PXDNL	ENST00000356297.5	c.1128C>T	p.His376His	synonymous_variant	Exon 10 of 23	1	NM_144651.5	ENSP00000348645.4

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124107 AN: 152046 Hom.: 52892 Cov.: 32

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.989

Gnomad AMR AF: 0.891

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.943

Gnomad OTH AF: 0.831

GnomAD2 exomes AF: 0.881 AC: 219671 AN: 249236 AF XY: 0.886

Gnomad AFR exome AF: 0.544

Gnomad AMR exome AF: 0.930

Gnomad ASJ exome AF: 0.915

Gnomad EAS exome AF: 0.689

Gnomad FIN exome AF: 0.925

Gnomad NFE exome AF: 0.938

Gnomad OTH exome AF: 0.891

GnomAD4 exome AF: 0.921 AC: 1345508 AN: 1461614 Hom.: 623913 Cov.: 65 AF XY: 0.920 AC XY: 668901 AN XY: 727086

African (AFR) AF: 0.538 AC: 18008 AN: 33466

American (AMR) AF: 0.925 AC: 41389 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.918 AC: 23996 AN: 26136

East Asian (EAS) AF: 0.696 AC: 27612 AN: 39694

South Asian (SAS) AF: 0.858 AC: 74035 AN: 86254

European-Finnish (FIN) AF: 0.927 AC: 49516 AN: 53400

Middle Eastern (MID) AF: 0.837 AC: 4826 AN: 5768

European-Non Finnish (NFE) AF: 0.947 AC: 1052561 AN: 1111800

Other (OTH) AF: 0.887 AC: 53565 AN: 60372

GnomAD4 genome AF: 0.816 AC: 124164 AN: 152164 Hom.: 52908 Cov.: 32 AF XY: 0.816 AC XY: 60675 AN XY: 74394

African (AFR) AF: 0.553 AC: 22938 AN: 41450

American (AMR) AF: 0.892 AC: 13641 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 3150 AN: 3472

East Asian (EAS) AF: 0.684 AC: 3525 AN: 5156

South Asian (SAS) AF: 0.852 AC: 4117 AN: 4830

European-Finnish (FIN) AF: 0.919 AC: 9743 AN: 10604

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.943 AC: 64151 AN: 68032

Other (OTH) AF: 0.831 AC: 1756 AN: 2114

Alfa AF: 0.881 Hom.: 42875

Bravo AF: 0.802

Asia WGS AF: 0.737 AC: 2565 AN: 3478

EpiCase AF: 0.937

EpiControl AF: 0.933

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

Oct 17, 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	-0.72
CADD	Benign	1.3
DANN	Benign	0.44
PhyloP100		1.8
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: rs6473599; hg19: chr8-52366200; COSMIC: COSV62491498;