rs1143016

Positions:

• chr1-2408773-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002617.4(PEX10):​c.279C>T​(p.Gly93=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0599 in 1,613,860 control chromosomes in the GnomAD database, including 3,773 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (367 hom., cov: 32)
  • Exomes 𝑓: 0.061 (3406 hom.)
• Consequence: PEX10 NM_002617.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -2.17

Genes affected

PEX10 (HGNC:8851): (peroxisomal biogenesis factor 10) This gene encodes a protein involved in import of peroxisomal matrix proteins. This protein localizes to the peroxisomal membrane. Mutations in this gene result in phenotypes within the Zellweger spectrum of peroxisomal biogenesis disorders, ranging from neonatal adrenoleukodystrophy to Zellweger syndrome. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-2408773-G-A is Benign according to our data. Variant chr1-2408773-G-A is described in ClinVar as [Benign]. Clinvar id is 129883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-2408773-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-2.17 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX10	NM_002617.4	c.279C>T	p.Gly93=	synonymous_variant	3/6	ENST00000447513.7	NP_002608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX10	ENST00000447513.7	c.279C>T	p.Gly93=	synonymous_variant	3/6	1	NM_002617.4	ENSP00000407922	P4

Frequencies

GnomAD3 genomes AF: 0.0502 AC: 7639 AN: 152138 Hom.: 367 Cov.: 32

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0217

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0368

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0677

Gnomad OTH AF: 0.0330

GnomAD3 exomes AF: 0.0536 AC: 13438 AN: 250712 Hom.: 609 AF XY: 0.0542 AC XY: 7354 AN XY: 135716

Gnomad AFR exome AF: 0.0115

Gnomad AMR exome AF: 0.0215

Gnomad ASJ exome AF: 0.0283

Gnomad EAS exome AF: 0.00125

Gnomad SAS exome AF: 0.0317

Gnomad FIN exome AF: 0.165

Gnomad NFE exome AF: 0.0651

Gnomad OTH exome AF: 0.0490

GnomAD4 exome AF: 0.0609 AC: 89014 AN: 1461604 Hom.: 3406 Cov.: 36 AF XY: 0.0605 AC XY: 44007 AN XY: 727134

Gnomad4 AFR exome AF: 0.00851

Gnomad4 AMR exome AF: 0.0208

Gnomad4 ASJ exome AF: 0.0289

Gnomad4 EAS exome AF: 0.00123

Gnomad4 SAS exome AF: 0.0354

Gnomad4 FIN exome AF: 0.157

Gnomad4 NFE exome AF: 0.0651

Gnomad4 OTH exome AF: 0.0513

GnomAD4 genome AF: 0.0502 AC: 7641 AN: 152256 Hom.: 367 Cov.: 32 AF XY: 0.0546 AC XY: 4063 AN XY: 74434

Gnomad4 AFR AF: 0.0102

Gnomad4 AMR AF: 0.0218

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0371

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.0677

Gnomad4 OTH AF: 0.0327

Alfa AF: 0.0560 Hom.: 142

Bravo AF: 0.0374

Asia WGS AF: 0.0180 AC: 61 AN: 3478

EpiCase AF: 0.0607

EpiControl AF: 0.0573

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Peroxisome biogenesis disorder 6A (Zellweger) Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 08, 2021	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 20, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Peroxisome biogenesis disorder 6B Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 08, 2021

- -

Zellweger spectrum disorders Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Nov 22, 2019

- -

Peroxisome biogenesis disorder, complementation group 7 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.29
DANN	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1143016; hg19: chr1-2340212;