6-143451036-CCTAAAGATGCTGAGGT-C

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_003630.3(PEX3):​c.-4_12delAAAGATGCTGAGGTCT​(p.Met1fs) variant causes a frameshift, start lost change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PEX3
NM_003630.3 frameshift, start_lost

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 7.65
Variant links:
Genes affected
PEX3 (HGNC:8858): (peroxisomal biogenesis factor 3) The product of this gene is involved in peroxisome biosynthesis and integrity. It assembles membrane vesicles before the matrix proteins are translocated. Peroxins (PEXs) are proteins that are essential for the assembly of functional peroxisomes. The peroxisome biogenesis disorders (PBDs) are a group of genetically heterogeneous autosomal recessive, lethal diseases characterized by multiple defects in peroxisome function. The peroxisomal biogenesis disorders are a heterogeneous group with at least 14 complementation groups and with more than 1 phenotype being observed in cases falling into particular complementation groups. Although the clinical features of PBD patients vary, cells from all PBD patients exhibit a defect in the import of one or more classes of peroxisomal matrix proteins into the organelle. Defects in this gene are a cause Zellweger syndrome (ZWS). [provided by RefSeq, Oct 2008]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 21 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 6-143451036-CCTAAAGATGCTGAGGT-C is Pathogenic according to our data. Variant chr6-143451036-CCTAAAGATGCTGAGGT-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3593211.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PEX3NM_003630.3 linkc.-4_12delAAAGATGCTGAGGTCT p.Met1fs frameshift_variant, start_lost Exon 1 of 12 ENST00000367591.5 NP_003621.1 P56589
PEX3NM_003630.3 linkc.-4_12delAAAGATGCTGAGGTCT 5_prime_UTR_variant Exon 1 of 12 ENST00000367591.5 NP_003621.1 P56589

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PEX3ENST00000367591.5 linkc.-4_12delAAAGATGCTGAGGTCT p.Met1fs frameshift_variant, start_lost Exon 1 of 12 1 NM_003630.3 ENSP00000356563.4 P56589
PEX3ENST00000367591 linkc.-4_12delAAAGATGCTGAGGTCT 5_prime_UTR_variant Exon 1 of 12 1 NM_003630.3 ENSP00000356563.4 P56589
PEX3ENST00000367592.5 linkc.-4_12delAAAGATGCTGAGGTCT p.Met1fs frameshift_variant, start_lost Exon 1 of 7 5 ENSP00000356564.1 Q7Z6V3
PEX3ENST00000367592 linkc.-4_12delAAAGATGCTGAGGTCT 5_prime_UTR_variant Exon 1 of 7 5 ENSP00000356564.1 Q7Z6V3

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Peroxisome biogenesis disorder 10A (Zellweger);C4479254:Peroxisome biogenesis disorder 10B Pathogenic:1
Jan 09, 2024
Fulgent Genetics, Fulgent Genetics
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-143772173; API