7-92499847-C-CAAAAAAAAAA

Variant names:

• chr7-92499847-C-CAAAAAAAAAA
• rs5885806
• NM_000466.3:c.2584-19_2584-10dupTTTTTTTTTT

Variant summary

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

The NM_000466.3(PEX1):​c.2584-19_2584-10dupTTTTTTTTTT variant causes a intron change. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: PEX1 NM_000466.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.05
• 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: Ambry Genetics, Myriad Women’s Health
• Heimler syndrome 1

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: 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 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000466.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX1	NM_000466.3	MANE Select	c.2584-19_2584-10dupTTTTTTTTTT		intron	N/A	NP_000457.1	O43933-1
	PEX1	NM_001282677.2		c.2413-19_2413-10dupTTTTTTTTTT		intron	N/A	NP_001269606.1	A0A0C4DG33
	PEX1	NM_001282678.2		c.1960-19_1960-10dupTTTTTTTTTT		intron	N/A	NP_001269607.1	B4DER6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX1	ENST00000248633.9	TSL:1 MANE Select	c.2584-10_2584-9insTTTTTTTTTT		intron	N/A	ENSP00000248633.4	O43933-1
	PEX1	ENST00000428214.5	TSL:1	c.2413-10_2413-9insTTTTTTTTTT		intron	N/A	ENSP00000394413.1	A0A0C4DG33
	PEX1	ENST00000951788.1		c.2584-10_2584-9insTTTTTTTTTT		intron	N/A	ENSP00000621847.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 8.48e-7 AC: 1 AN: 1178976 Hom.: 0 Cov.: 0 AF XY: 0.00000169 AC XY: 1 AN XY: 592152

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28676

American (AMR) AF: 0.00 AC: 0 AN: 38784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22446

East Asian (EAS) AF: 0.00 AC: 0 AN: 35474

South Asian (SAS) AF: 0.00 AC: 0 AN: 72424

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44984

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4990

European-Non Finnish (NFE) AF: 0.00000113 AC: 1 AN: 881420

Other (OTH) AF: 0.00 AC: 0 AN: 49778

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs5885806; hg19: chr7-92129161;