Variant 8-51339760-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_144651.5(PXDNL):c.4017-7T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,583,850 control chromosomes in the GnomAD database, including 41,399 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.22 ( 3864 hom., cov: 33)

Exomes 𝑓: 0.23 ( 37535 hom. )

Consequence

PXDNL
NM_144651.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0002225

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0570

Variant links:

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]

PXDNL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 8-51339760-A-G is Benign according to our data. Variant chr8-51339760-A-G is described in ClinVar as [Benign]. Clinvar id is 3059469.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXDNL	NM_144651.5 linkuse as main transcript	c.4017-7T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000356297.5	NP_653252.4

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PXDNL	ENST00000356297.5 linkuse as main transcript	c.4017-7T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_144651.5	ENSP00000348645	P1	A1KZ92-1
PXDNL	ENST00000522933.5 linkuse as main transcript	c.1238-7T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000428114
PXDNL	ENST00000519183.1 linkuse as main transcript	n.426T>C	non_coding_transcript_exon_variant	1/3	3
PXDNL	ENST00000522628.5 linkuse as main transcript	c.1700-18863T>C	intron_variant, NMD_transcript_variant		2		ENSP00000429855

Frequencies

GnomAD3 genomes

AF:

0.221

AC:

33559

AN:

152028

Hom.:

3858

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.231

Gnomad EAS

AF:

0.0593

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.224

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.236

Gnomad OTH

AF:

0.232

GnomAD3 exomes

AF:

0.206

AC:

46020

AN:

223314

Hom.:

5161

AF XY:

0.207

AC XY:

25131

AN XY:

121324

show subpopulations

Gnomad AFR exome

AF:

0.239

Gnomad AMR exome

AF:

0.168

Gnomad ASJ exome

AF:

0.233

Gnomad EAS exome

AF:

0.0544

Gnomad SAS exome

AF:

0.177

Gnomad FIN exome

AF:

0.223

Gnomad NFE exome

AF:

0.235

Gnomad OTH exome

AF:

0.218

GnomAD4 exome

AF:

0.225

AC:

322579

AN:

1431704

Hom.:

37535

Cov.:

AF XY:

0.224

AC XY:

159442

AN XY:

710978

show subpopulations

Gnomad4 AFR exome

AF:

0.242

Gnomad4 AMR exome

AF:

0.162

Gnomad4 ASJ exome

AF:

0.229

Gnomad4 EAS exome

AF:

0.0667

Gnomad4 SAS exome

AF:

0.179

Gnomad4 FIN exome

AF:

0.224

Gnomad4 NFE exome

AF:

0.236

Gnomad4 OTH exome

AF:

0.221

GnomAD4 genome

AF:

0.221

AC:

33591

AN:

152146

Hom.:

3864

Cov.:

AF XY:

0.217

AC XY:

16140

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.235

Gnomad4 AMR

AF:

0.181

Gnomad4 ASJ

AF:

0.231

Gnomad4 EAS

AF:

0.0590

Gnomad4 SAS

AF:

0.180

Gnomad4 FIN

AF:

0.224

Gnomad4 NFE

AF:

0.236

Gnomad4 OTH

AF:

0.233

Alfa

AF:

0.226

Hom.:

1787

Bravo

AF:

0.216

Asia WGS

AF:

0.168

AC:

586

AN:

3478

EpiCase

AF:

0.232

EpiControl

AF:

0.231

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PXDNL-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 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

-0.85

CADD

Benign

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00022

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.19

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over