chr7-92528434-A-T
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PS1_ModeratePM2
The NM_000466.3(PEX1):c.2T>A(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.00000126 in 1,587,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Consequence
PEX1
NM_000466.3 start_lost
NM_000466.3 start_lost
Scores
8
4
3
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 3.87
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Start lost variant, no new inframe start found.
PS1
Another start lost variant in NM_000466.3 (PEX1) was described as [Likely_pathogenic] in ClinVar as 189106
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PEX1 | NM_000466.3 | c.2T>A | p.Met1? | start_lost | 1/24 | ENST00000248633.9 | |
PEX1 | NM_001282677.2 | c.2T>A | p.Met1? | start_lost | 1/23 | ||
PEX1 | XM_047420472.1 | c.2T>A | p.Met1? | start_lost | 1/23 | ||
PEX1 | NM_001282678.2 | c.-658T>A | 5_prime_UTR_variant | 1/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX1 | ENST00000248633.9 | c.2T>A | p.Met1? | start_lost | 1/24 | 1 | NM_000466.3 | P1 | |
PEX1 | ENST00000428214.5 | c.2T>A | p.Met1? | start_lost | 1/23 | 1 | |||
PEX1 | ENST00000438045.5 | c.2T>A | p.Met1? | start_lost | 1/21 | 2 | |||
PEX1 | ENST00000484913.5 | n.6T>A | non_coding_transcript_exon_variant | 1/24 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152084Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 6.97e-7 AC: 1AN: 1435574Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1AN XY: 711776
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 152084Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74306
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D
PROVEAN
Benign
N;N;N
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
0.98
.;D;.
Vest4
MutPred
Loss of stability (P = 0.0076);Loss of stability (P = 0.0076);Loss of stability (P = 0.0076);
MVP
ClinPred
D
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at