rs62653598

chr7-92518164-TGTTGATCAACCCAAA-TTTGC

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_000466.3(PEX1):c.434_448delinsGCAA(p.Val145GlyfsTer24) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.94

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]

ACMG classification

Verdict is Pathogenic. Variant got 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/exons	MANE	UniProt
PEX1	NM_000466.3	c.434_448delinsGCAA	p.Val145GlyfsTer24	frameshift_variant	4/24	ENST00000248633.9
PEX1	NM_001282677.2	c.434_448delinsGCAA	p.Val145GlyfsTer24	frameshift_variant	4/23
PEX1	XM_047420472.1	c.434_448delinsGCAA	p.Val145GlyfsTer24	frameshift_variant	4/23
PEX1	NM_001282678.2	c.-191_-177delinsGCAA		5_prime_UTR_variant	4/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX1	ENST00000248633.9	c.434_448delinsGCAA	p.Val145GlyfsTer24	frameshift_variant	4/24	1	NM_000466.3	P1
PEX1	ENST00000428214.5	c.434_448delinsGCAA	p.Val145GlyfsTer24	frameshift_variant	4/23	1
PEX1	ENST00000438045.5	c.273+3923_273+3937delinsGCAA		intron_variant		2
PEX1	ENST00000484913.5	n.473_487delinsGCAA		non_coding_transcript_exon_variant	4/24	2

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs62653598; hg19: chr7-92147479;