rs3762000

Variant names:

• chr6-143470941-C-G
• rs3762000
• NM_003630.3:c.332-20C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-143470941-C-G
• chr6-143470941-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003630.3(PEX3):​c.332-20C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,599,828 control chromosomes in the GnomAD database, including 51,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8652 hom., cov: 32)
  • Exomes 𝑓: 0.24 (43308 hom.)
• Consequence: PEX3 NM_003630.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.143
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-143470941-C-G is Benign according to our data. Variant chr6-143470941-C-G is described in ClinVar as Benign. ClinVar VariationId is 167458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 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.332-20C>G		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.332-20C>G		intron	N/A	ENSP00000356563.4
	PEX3	ENST00000367592.5	TSL:5	c.200-20C>G		intron	N/A	ENSP00000356564.1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47937 AN: 151880 Hom.: 8620 Cov.: 32

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.282

GnomAD2 exomes AF: 0.269 AC: 67245 AN: 249884 AF XY: 0.263

Gnomad AFR exome AF: 0.499

Gnomad AMR exome AF: 0.277

Gnomad ASJ exome AF: 0.335

Gnomad EAS exome AF: 0.220

Gnomad FIN exome AF: 0.352

Gnomad NFE exome AF: 0.226

Gnomad OTH exome AF: 0.243

GnomAD4 exome AF: 0.237 AC: 343126 AN: 1447830 Hom.: 43308 Cov.: 29 AF XY: 0.237 AC XY: 171067 AN XY: 721102

African (AFR) AF: 0.511 AC: 16880 AN: 33030

American (AMR) AF: 0.275 AC: 12281 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 8748 AN: 25990

East Asian (EAS) AF: 0.262 AC: 10367 AN: 39494

South Asian (SAS) AF: 0.252 AC: 21687 AN: 85924

European-Finnish (FIN) AF: 0.344 AC: 18123 AN: 52720

Middle Eastern (MID) AF: 0.221 AC: 1260 AN: 5702

European-Non Finnish (NFE) AF: 0.217 AC: 238838 AN: 1100432

Other (OTH) AF: 0.250 AC: 14942 AN: 59882

GnomAD4 genome AF: 0.316 AC: 48016 AN: 151998 Hom.: 8652 Cov.: 32 AF XY: 0.318 AC XY: 23641 AN XY: 74290

African (AFR) AF: 0.495 AC: 20533 AN: 41442

American (AMR) AF: 0.265 AC: 4046 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1223 AN: 3466

East Asian (EAS) AF: 0.218 AC: 1127 AN: 5180

South Asian (SAS) AF: 0.244 AC: 1178 AN: 4822

European-Finnish (FIN) AF: 0.366 AC: 3861 AN: 10548

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15262 AN: 67938

Other (OTH) AF: 0.285 AC: 601 AN: 2106

Alfa AF: 0.281 Hom.: 1249

Bravo AF: 0.316

Asia WGS AF: 0.257 AC: 896 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.64
DANN	Benign	0.54
PhyloP100		-0.14
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: rs3762000; hg19: chr6-143792078; COSMIC: COSV62567907;