6-143450867-C-CG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003630.3(PEX3):​c.-175dupG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PEX3
NM_003630.3 5_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47
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]
ADAT2 (HGNC:21172): (adenosine deaminase tRNA specific 2) Predicted to enable tRNA-specific adenosine-34 deaminase activity. Predicted to be involved in tRNA wobble adenosine to inosine editing. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PEX3NM_003630.3 linkc.-175dupG 5_prime_UTR_variant Exon 1 of 12 ENST00000367591.5 NP_003621.1 P56589
ADAT2NM_182503.3 linkc.-210dupC upstream_gene_variant ENST00000237283.9 NP_872309.2 Q7Z6V5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PEX3ENST00000367591 linkc.-175dupG 5_prime_UTR_variant Exon 1 of 12 1 NM_003630.3 ENSP00000356563.4 P56589
PEX3ENST00000367592 linkc.-175dupG 5_prime_UTR_variant Exon 1 of 7 5 ENSP00000356564.1 Q7Z6V3
ADAT2ENST00000237283.9 linkc.-210dupC upstream_gene_variant 1 NM_182503.3 ENSP00000237283.8 Q7Z6V5-1
ADAT2ENST00000367593.1 linkn.-195dupC upstream_gene_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
7
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

Peroxisome biogenesis disorder 1A (Zellweger) Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs886061130; hg19: chr6-143772004; API