NM_000466.3:c.781C>T

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2

The NM_000466.3(PEX1):​c.781C>T​(p.Gln261*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

PEX1
NM_000466.3 stop_gained

Scores

1
2
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.37

Publications

0 publications found
Variant links:
Genes affected
PEX1 (HGNC:8850): (peroxisomal biogenesis factor 1) This gene encodes a member of the AAA ATPase family, a large group of ATPases associated with diverse cellular activities. This protein is cytoplasmic but is often anchored to a peroxisomal membrane where it forms a heteromeric complex and plays a role in the import of proteins into peroxisomes and peroxisome biogenesis. Mutations in this gene have been associated with complementation group 1 peroxisomal disorders such as neonatal adrenoleukodystrophy, infantile Refsum disease, and Zellweger syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2013]
PEX1 Gene-Disease associations (from GenCC):
  • peroxisome biogenesis disorder
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
  • peroxisome biogenesis disorder 1A (Zellweger)
    Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health, Ambry Genetics
  • Heimler syndrome 1
    Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, G2P, Ambry Genetics
  • peroxisome biogenesis disorder 1B
    Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
  • Zellweger spectrum disorders
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 10 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PEX1NM_000466.3 linkc.781C>T p.Gln261* stop_gained Exon 5 of 24 ENST00000248633.9 NP_000457.1 O43933-1
PEX1NM_001282677.2 linkc.781C>T p.Gln261* stop_gained Exon 5 of 23 NP_001269606.1 O43933A0A0C4DG33
PEX1NM_001282678.2 linkc.157C>T p.Gln53* stop_gained Exon 5 of 24 NP_001269607.1 O43933B4DER6
PEX1XM_047420472.1 linkc.781C>T p.Gln261* stop_gained Exon 5 of 23 XP_047276428.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PEX1ENST00000248633.9 linkc.781C>T p.Gln261* stop_gained Exon 5 of 24 1 NM_000466.3 ENSP00000248633.4 O43933-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Uncertain
0.090
CADD
Pathogenic
32
DANN
Uncertain
1.0
Eigen
Benign
0.16
Eigen_PC
Benign
-0.076
FATHMM_MKL
Benign
0.73
D
PhyloP100
1.4
Vest4
0.56
GERP RS
2.1
Mutation Taster
=1/199
disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs61750403; hg19: chr7-92147048; API