6-143462894-ATT-AT

Variant names:

• chr6-143462894-AT-A
• rs397705490
• NM_003630.3:c.206-14delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_003630.3(PEX3):​c.206-14delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.69 (36245 hom., cov: 0)
  • Exomes 𝑓: 0.64 (292704 hom.)
• Consequence: PEX3 NM_003630.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0500
• Publications: 1 publications found

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]

PEX3 Gene-Disease associations (from GenCC):

• peroxisome biogenesis disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• peroxisome biogenesis disorder 10A (Zellweger)

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• peroxisome biogenesis disorder 10B

  Inheritance: AR Classification: STRONG Submitted by: G2P
• Zellweger spectrum disorders

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 6-143462894-AT-A is Benign according to our data. Variant chr6-143462894-AT-A is described in ClinVar as Benign. ClinVar VariationId is 259105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003630.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX3	NM_003630.3	MANE Select	c.206-14delT		intron	N/A	NP_003621.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX3	ENST00000367591.5	TSL:1 MANE Select	c.206-21delT		intron	N/A	ENSP00000356563.4
	PEX3	ENST00000367592.5	TSL:5	c.74-21delT		intron	N/A	ENSP00000356564.1

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104205 AN: 151652 Hom.: 36192 Cov.: 0

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.679

GnomAD2 exomes AF: 0.650 AC: 163046 AN: 250758 AF XY: 0.639

Gnomad AFR exome AF: 0.782

Gnomad AMR exome AF: 0.737

Gnomad ASJ exome AF: 0.694

Gnomad EAS exome AF: 0.549

Gnomad FIN exome AF: 0.697

Gnomad NFE exome AF: 0.646

Gnomad OTH exome AF: 0.644

GnomAD4 exome AF: 0.636 AC: 911409 AN: 1433936 Hom.: 292704 Cov.: 0 AF XY: 0.632 AC XY: 452098 AN XY: 715350

African (AFR) AF: 0.788 AC: 25918 AN: 32878

American (AMR) AF: 0.734 AC: 32782 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 18112 AN: 25972

East Asian (EAS) AF: 0.611 AC: 24159 AN: 39520

South Asian (SAS) AF: 0.508 AC: 43516 AN: 85634

European-Finnish (FIN) AF: 0.696 AC: 37176 AN: 53382

Middle Eastern (MID) AF: 0.635 AC: 3631 AN: 5718

European-Non Finnish (NFE) AF: 0.634 AC: 688544 AN: 1086774

Other (OTH) AF: 0.632 AC: 37571 AN: 59416

GnomAD4 genome AF: 0.687 AC: 104314 AN: 151768 Hom.: 36245 Cov.: 0 AF XY: 0.687 AC XY: 50975 AN XY: 74180

African (AFR) AF: 0.781 AC: 32302 AN: 41374

American (AMR) AF: 0.723 AC: 11034 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2423 AN: 3468

East Asian (EAS) AF: 0.552 AC: 2845 AN: 5152

South Asian (SAS) AF: 0.498 AC: 2397 AN: 4812

European-Finnish (FIN) AF: 0.704 AC: 7405 AN: 10518

Middle Eastern (MID) AF: 0.606 AC: 177 AN: 292

European-Non Finnish (NFE) AF: 0.643 AC: 43679 AN: 67884

Other (OTH) AF: 0.680 AC: 1429 AN: 2100

Alfa AF: 0.605 Hom.: 3352

Bravo AF: 0.696

Asia WGS AF: 0.543 AC: 1890 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Peroxisome biogenesis disorder 10B Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Peroxisome biogenesis disorder 10A (Zellweger) Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Mar 03, 2022

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.050
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs397705490; hg19: chr6-143784031; COSMIC: COSV107477832;