NM_000466.3:c.1906_2064del

Variant names:

• chr7-92504738-CAAGCCGCTGGCTCTGCACCGCATCAGGACTGTGCTCATGTTCCGGGACAGCAGGCAGTCCAGCAATGAGGTCAAGGTCATCCAGCAGGACAACAGATGGCTGCATCCACACTGCCTCTGAGAAAGCCACCTCTAGGGTTTTTTGTATGTTTTCAAGCCT-C
• rs1554372074
• NM_000466.3:c.1906_2064del

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM4 PP3 PP5

The NM_000466.3(PEX1):​c.1906_2064del​(p.Arg636_Leu688del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PEX1 NM_000466.3 conservative_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.73
• Publications: 0 publications found

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

ENSG00000244055 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_000466.3.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 7-92504738-CAAGCCGCTGGCTCTGCACCGCATCAGGACTGTGCTCATGTTCCGGGACAGCAGGCAGTCCAGCAATGAGGTCAAGGTCATCCAGCAGGACAACAGATGGCTGCATCCACACTGCCTCTGAGAAAGCCACCTCTAGGGTTTTTTGTATGTTTTCAAGCCT-C is Pathogenic according to our data. Variant chr7-92504738-CAAGCCGCTGGCTCTGCACCGCATCAGGACTGTGCTCATGTTCCGGGACAGCAGGCAGTCCAGCAATGAGGTCAAGGTCATCCAGCAGGACAACAGATGGCTGCATCCACACTGCCTCTGAGAAAGCCACCTCTAGGGTTTTTTGTATGTTTTCAAGCCT-C is described in ClinVar as Pathogenic. ClinVar VariationId is 7518.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX1	NM_000466.3	c.1906_2064del	p.Arg636_Leu688del	conservative_inframe_deletion	Exon 12 of 24	ENST00000248633.9	NP_000457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX1	ENST00000248633.9	c.1906_2064del	p.Arg636_Leu688del	conservative_inframe_deletion	Exon 12 of 24	1	NM_000466.3	ENSP00000248633.4

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Peroxisome biogenesis disorder 1A (Zellweger) Pathogenic:1

Apr 14, 1998

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.7

Splicing

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

Other links and lift over

dbSNP: rs1554372074; hg19: chr7-92134052;