6-143479155-C-A

Variant names:

• chr6-143479155-C-A
• rs201179294
• NM_003630.3:c.898C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003630.3(PEX3):​c.898C>A​(p.Arg300Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,451,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PEX3 NM_003630.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61
• Publications: 0 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX3	NM_003630.3	MANE Select	c.898C>A	p.Arg300Arg	synonymous	Exon 10 of 12	NP_003621.1	P56589

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX3	ENST00000367591.5	TSL:1 MANE Select	c.898C>A	p.Arg300Arg	synonymous	Exon 10 of 12	ENSP00000356563.4	P56589
	PEX3	ENST00000918413.1		c.895C>A	p.Arg299Arg	synonymous	Exon 10 of 12	ENSP00000588472.1
	PEX3	ENST00000918414.1		c.724C>A	p.Arg242Arg	synonymous	Exon 9 of 11	ENSP00000588473.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1451552 Hom.: 0 Cov.: 26 AF XY: 0.00000138 AC XY: 1 AN XY: 722918

African (AFR) AF: 0.00 AC: 0 AN: 33240

American (AMR) AF: 0.00 AC: 0 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26046

East Asian (EAS) AF: 0.00 AC: 0 AN: 39530

South Asian (SAS) AF: 0.00 AC: 0 AN: 86024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1102870

Other (OTH) AF: 0.00 AC: 0 AN: 60024

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	8.9
DANN	Benign	0.64
PhyloP100		1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.39		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.39		Position offset: 43

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

Other links and lift over

dbSNP: rs201179294; hg19: chr6-143800292;