Variant 6-143451174-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.29

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
PEX3	NM_003630.3 link	c.73+59C>T		intron_variant		ENST00000367591.5	NP_003621.1	P56589

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX3	ENST00000367591.5 link	c.73+59C>T		intron_variant		1	NM_003630.3	ENSP00000356563.4		P56589
PEX3	ENST00000367592.5 link	c.73+59C>T		intron_variant		5		ENSP00000356564.1		Q7Z6V3

Frequencies

GnomAD3 genomes

AF:

0.272

AC:

41182

AN:

151656

Hom.:

5978

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.276

AC XY:

20438

AN XY:

74158

show subpopulations

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

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 11, 2018

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over