6-143451174-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003630.3(PEX3):c.73+59C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,178,394 control chromosomes in the GnomAD database, including 34,940 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (5992 hom., cov: 31)
  • Exomes 𝑓: 0.23 (28948 hom.)
• Consequence: PEX3 NM_003630.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.29

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 6-143451174-C-T is Benign according to our data. Variant chr6-143451174-C-T is described in ClinVar as [Benign]. Clinvar id is 1227796.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEX3	NM_003630.3	c.73+59C>T		intron_variant		ENST00000367591.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX3	ENST00000367591.5	c.73+59C>T		intron_variant		1	NM_003630.3	P1
PEX3	ENST00000367592.5	c.73+59C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41182 AN: 151656 Hom.: 5978 Cov.: 31

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.247

GnomAD4 exome AF: 0.229 AC: 235514 AN: 1026620 Hom.: 28948 AF XY: 0.229 AC XY: 121368 AN XY: 530730

Gnomad4 AFR exome AF: 0.366

Gnomad4 AMR exome AF: 0.265

Gnomad4 ASJ exome AF: 0.322

Gnomad4 EAS exome AF: 0.243

Gnomad4 SAS exome AF: 0.227

Gnomad4 FIN exome AF: 0.343

Gnomad4 NFE exome AF: 0.211

Gnomad4 OTH exome AF: 0.235

GnomAD4 genome AF: 0.272 AC: 41235 AN: 151774 Hom.: 5992 Cov.: 31 AF XY: 0.276 AC XY: 20438 AN XY: 74158

Gnomad4 AFR AF: 0.363

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.251

Alfa AF: 0.226 Hom.: 3909

Bravo AF: 0.267

Asia WGS AF: 0.236 AC: 823 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 11, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	0.33
Dann	Benign	0.92

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

Publications

LitVar

Other links and lift over

dbSNP: rs2272924; hg19: chr6-143772311; COSMIC: COSV52793675; COSMIC: COSV52793675;