7-92499847-C-CAA

Variant names:

• chr7-92499847-C-CAA
• rs5885806
• NM_000466.3:c.2584-11_2584-10dupTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_000466.3(PEX1):​c.2584-11_2584-10dupTT variant causes a intron change. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00029 (0 hom.)
• Consequence: PEX1 NM_000466.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.05
• Publications: 6 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: Benign. The variant received -8 ACMG points.

• BP6: Variant 7-92499847-C-CAA is Benign according to our data. Variant chr7-92499847-C-CAA is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1164265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.2584-11_2584-10dupTT		intron	N/A	NP_000457.1	O43933-1
	PEX1	NM_001282677.2		c.2413-11_2413-10dupTT		intron	N/A	NP_001269606.1	A0A0C4DG33
	PEX1	NM_001282678.2		c.1960-11_1960-10dupTT		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_2584-9insTT		intron	N/A	ENSP00000248633.4	O43933-1
	PEX1	ENST00000428214.5	TSL:1	c.2413-10_2413-9insTT		intron	N/A	ENSP00000394413.1	A0A0C4DG33
	PEX1	ENST00000951788.1		c.2584-10_2584-9insTT		intron	N/A	ENSP00000621847.1

Frequencies

GnomAD3 genomes AF: 0.000383 AC: 56 AN: 146164 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000204

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000451

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000260 AC: 40 AN: 153898 AF XY: 0.000197

Gnomad AFR exome AF: 0.00140

Gnomad AMR exome AF: 0.000228

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000821

Gnomad FIN exome AF: 0.0000741

Gnomad NFE exome AF: 0.000158

Gnomad OTH exome AF: 0.000549

GnomAD4 exome AF: 0.000294 AC: 347 AN: 1178500 Hom.: 0 Cov.: 0 AF XY: 0.000260 AC XY: 154 AN XY: 591950

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

African (AFR) AF: 0.00188 AC: 54 AN: 28650

American (AMR) AF: 0.000103 AC: 4 AN: 38784

Ashkenazi Jewish (ASJ) AF: 0.0000446 AC: 1 AN: 22446

East Asian (EAS) AF: 0.00 AC: 0 AN: 35464

South Asian (SAS) AF: 0.000110 AC: 8 AN: 72406

European-Finnish (FIN) AF: 0.000111 AC: 5 AN: 44972

Middle Eastern (MID) AF: 0.000200 AC: 1 AN: 4990

European-Non Finnish (NFE) AF: 0.000289 AC: 255 AN: 881028

Other (OTH) AF: 0.000382 AC: 19 AN: 49760

⚠️ 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 AF: 0.000390 AC: 57 AN: 146262 Hom.: 0 Cov.: 0 AF XY: 0.000421 AC XY: 30 AN XY: 71310

African (AFR) AF: 0.00130 AC: 51 AN: 39322

American (AMR) AF: 0.000203 AC: 3 AN: 14752

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3382

East Asian (EAS) AF: 0.00 AC: 0 AN: 4974

South Asian (SAS) AF: 0.00 AC: 0 AN: 4662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000452 AC: 3 AN: 66440

Other (OTH) AF: 0.00 AC: 0 AN: 2026

Alfa AF: 0.000288 Hom.: 1774

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Zellweger spectrum disorders (1)

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;