dbSNP rs201816215: PXDNL:p.Arg1408Leu (chr8-51320821-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144651.5(PXDNL):c.4223G>T(p.Arg1408Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,564 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R1408H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

PXDNL
NM_144651.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.212

Publications

4 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08004564).

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.4223G>T	p.Arg1408Leu	missense	Exon 22 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.4223G>T	p.Arg1408Leu	missense	Exon 22 of 23	ENSP00000348645.4	A1KZ92-1
PXDNL	ENST00000894552.1		c.4403G>T	p.Arg1468Leu	missense	Exon 23 of 24	ENSP00000564611.1
PXDNL	ENST00000894549.1		c.4151G>T	p.Arg1384Leu	missense	Exon 21 of 22	ENSP00000564608.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000805

AC:

AN:

248590

AF XY:

0.00000741

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461564

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727078

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111786

Other (OTH)

AF:

0.00

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.33

CADD

Benign

2.9

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0067

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.58

M_CAP

Benign

0.0096

MetaRNN

Benign

0.080

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.4

PhyloP100

0.21

PrimateAI

Benign

0.19

PROVEAN

Benign

-2.0

REVEL

Benign

0.20

Sift

Benign

0.26

Sift4G

Benign

0.24

Polyphen

0.17

Vest4

0.20

MutPred

0.48

Loss of disorder (P = 0.0281)

MVP

0.18

MPC

0.23

ClinPred

0.11

GERP RS

-5.5

Varity_R

0.097

gMVP

0.69

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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