Variant 8-51319989-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144651.5(PXDNL):c.4294C>T(p.Pro1432Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,416,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PXDNL
NM_144651.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.580

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.093887895).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXDNL	NM_144651.5 linkuse as main transcript	c.4294C>T	p.Pro1432Ser	missense_variant	23/23	ENST00000356297.5	NP_653252.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PXDNL	ENST00000356297.5 linkuse as main transcript	c.4294C>T	p.Pro1432Ser	missense_variant	23/23	1	NM_144651.5	ENSP00000348645	P1	A1KZ92-1
	ENST00000521294.1 linkuse as main transcript	n.121-731G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000897

AC:

AN:

222902

Hom.:

AF XY:

0.00

AC XY:

AN XY:

121952

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000739

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000141

AC:

AN:

1416950

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

704646

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000524

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 05, 2023

The c.4294C>T (p.P1432S) alteration is located in exon 23 (coding exon 23) of the PXDNL gene. This alteration results from a C to T substitution at nucleotide position 4294, causing the proline (P) at amino acid position 1432 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.43

CADD

Benign

2.3

DANN

Benign

0.75

DEOGEN2

Benign

0.0065

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.71

M_CAP

Benign

0.019

MetaRNN

Benign

0.094

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-2.4

REVEL

Benign

0.099

Sift

Benign

0.45

Sift4G

Benign

0.37

Polyphen

0.045

Vest4

0.12

MutPred

0.59

Loss of catalytic residue at P1432 (P = 0.0135);

MVP

0.21

MPC

0.15

ClinPred

0.043

GERP RS

0.33

Varity_R

0.079

gMVP

0.76

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

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