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GeneBe

8-51339633-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_144651.5(PXDNL):c.4137C>A(p.Leu1379=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,613,180 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 13 hom., cov: 33)
Exomes 𝑓: 0.0013 ( 46 hom. )

Consequence

PXDNL
NM_144651.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.692
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-51339633-G-T is Benign according to our data. Variant chr8-51339633-G-T is described in ClinVar as [Benign]. Clinvar id is 3035044.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.692 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00221 (336/152344) while in subpopulation EAS AF= 0.0499 (259/5192). AF 95% confidence interval is 0.0449. There are 13 homozygotes in gnomad4. There are 191 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 13 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PXDNLNM_144651.5 linkuse as main transcriptc.4137C>A p.Leu1379= synonymous_variant 21/23 ENST00000356297.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PXDNLENST00000356297.5 linkuse as main transcriptc.4137C>A p.Leu1379= synonymous_variant 21/231 NM_144651.5 P1A1KZ92-1
PXDNLENST00000522933.5 linkuse as main transcriptc.1359C>A p.Leu453= synonymous_variant 4/65
PXDNLENST00000519183.1 linkuse as main transcriptn.553C>A non_coding_transcript_exon_variant 1/33
PXDNLENST00000522628.5 linkuse as main transcriptc.1700-18736C>A intron_variant, NMD_transcript_variant 2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00217
AC:
331
AN:
152226
Hom.:
13
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000434
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00111
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0498
Gnomad SAS
AF:
0.00579
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00382
GnomAD3 exomes
AF:
0.00440
AC:
1093
AN:
248228
Hom.:
35
AF XY:
0.00411
AC XY:
553
AN XY:
134644
show subpopulations
Gnomad AFR exome
AF:
0.000517
Gnomad AMR exome
AF:
0.000117
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0562
Gnomad SAS exome
AF:
0.00185
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000887
Gnomad OTH exome
AF:
0.00266
GnomAD4 exome
AF:
0.00132
AC:
1922
AN:
1460836
Hom.:
46
Cov.:
32
AF XY:
0.00136
AC XY:
991
AN XY:
726634
show subpopulations
Gnomad4 AFR exome
AF:
0.000239
Gnomad4 AMR exome
AF:
0.0000673
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0357
Gnomad4 SAS exome
AF:
0.00253
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000261
Gnomad4 OTH exome
AF:
0.00413
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00221
AC:
336
AN:
152344
Hom.:
13
Cov.:
33
AF XY:
0.00256
AC XY:
191
AN XY:
74502
show subpopulations
Gnomad4 AFR
AF:
0.000433
Gnomad4 AMR
AF:
0.00111
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0499
Gnomad4 SAS
AF:
0.00580
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00614
Alfa
AF:
0.000177
Hom.:
0
Bravo
AF:
0.00243
Asia WGS
AF:
0.0300
AC:
105
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

PXDNL-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesAug 20, 2019This 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
-0.79
Cadd
Benign
0.74
Dann
Benign
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs138123996; hg19: chr8-52252193; COSMIC: COSV62488472; API