rs284238

Positions:

• chr1-10618431-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004565.3(PEX14):​c.384+14A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,599,916 control chromosomes in the GnomAD database, including 18,358 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3289 hom., cov: 33)
  • Exomes 𝑓: 0.14 (15069 hom.)
• Consequence: PEX14 NM_004565.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.520

Genes affected

PEX14 (HGNC:8856): (peroxisomal biogenesis factor 14) This gene encodes an essential component of the peroxisomal import machinery. The protein is integrated into peroxisome membranes with its C-terminus exposed to the cytosol, and interacts with the cytosolic receptor for proteins containing a PTS1 peroxisomal targeting signal. The protein also functions as a transcriptional corepressor and interacts with a histone deacetylase. A mutation in this gene results in one form of Zellweger syndrome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-10618431-A-T is Benign according to our data. Variant chr1-10618431-A-T is described in ClinVar as [Benign]. Clinvar id is 95145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-10618431-A-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEX14	NM_004565.3	c.384+14A>T		intron_variant		ENST00000356607.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX14	ENST00000356607.9	c.384+14A>T		intron_variant		1	NM_004565.3	P1
PEX14	ENST00000491661.2	c.369+14A>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28931 AN: 152152 Hom.: 3269 Cov.: 33

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.0778

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.179

GnomAD3 exomes AF: 0.155 AC: 38508 AN: 248840 Hom.: 3471 AF XY: 0.157 AC XY: 21089 AN XY: 134738

Gnomad AFR exome AF: 0.311

Gnomad AMR exome AF: 0.104

Gnomad ASJ exome AF: 0.187

Gnomad EAS exome AF: 0.0889

Gnomad SAS exome AF: 0.197

Gnomad FIN exome AF: 0.235

Gnomad NFE exome AF: 0.130

Gnomad OTH exome AF: 0.151

GnomAD4 exome AF: 0.137 AC: 198517 AN: 1447646 Hom.: 15069 Cov.: 28 AF XY: 0.139 AC XY: 100463 AN XY: 721146

Gnomad4 AFR exome AF: 0.323

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.184

Gnomad4 EAS exome AF: 0.0726

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.149

GnomAD4 genome AF: 0.190 AC: 28992 AN: 152270 Hom.: 3289 Cov.: 33 AF XY: 0.196 AC XY: 14596 AN XY: 74466

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.0778

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.177

Alfa AF: 0.158 Hom.: 407

Bravo AF: 0.185

Asia WGS AF: 0.129 AC: 452 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 30, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 26, 2018	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 26, 2015	- -

Peroxisome biogenesis disorder, complementation group K Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Peroxisome biogenesis disorder 13A (Zellweger) Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.14
DANN	Benign	0.56
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: rs284238; hg19: chr1-10678488; COSMIC: COSV63061569; COSMIC: COSV63061569;