dbSNP rs369513519: PXDNL:p.Arg1463Leu (chr8-51319895-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_144651.5(PXDNL):c.4388G>T(p.Arg1463Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1463C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PXDNL
NM_144651.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.31

Publications

1 publications found

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:

ENSG00000253664 (HGNC:):

ENSG00000253664 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03924918).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144651.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXDNL	NM_144651.5	MANE Select	c.4388G>T	p.Arg1463Leu	missense	Exon 23 of 23	NP_653252.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PXDNL	ENST00000356297.5	TSL:1 MANE Select	c.4388G>T	p.Arg1463Leu	missense	Exon 23 of 23	ENSP00000348645.4	A1KZ92-1
PXDNL	ENST00000894552.1		c.4568G>T	p.Arg1523Leu	missense	Exon 24 of 24	ENSP00000564611.1
PXDNL	ENST00000894549.1		c.4316G>T	p.Arg1439Leu	missense	Exon 22 of 22	ENSP00000564608.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1373800

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

679738

African (AFR)

AF:

0.00

AC:

AN:

29702

American (AMR)

AF:

0.00

AC:

AN:

29266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22558

East Asian (EAS)

AF:

0.00

AC:

AN:

36514

South Asian (SAS)

AF:

0.00

AC:

AN:

72402

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51250

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5402

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1070504

Other (OTH)

AF:

0.00

AC:

AN:

56202

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.70

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0024

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0031

LIST_S2

Benign

0.60

M_CAP

Benign

0.021

MetaRNN

Benign

0.039

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-1.3

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.67

REVEL

Benign

0.14

Sift

Uncertain

0.014

Sift4G

Uncertain

0.026

Polyphen

0.0010

Vest4

0.097

MutPred

0.20

Gain of stability (P = 0.0061)

MVP

0.067

MPC

0.45

ClinPred

0.25

GERP RS

-8.7

Varity_R

0.051

gMVP

0.66

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over