rs12375

Positions:

chr1-10536284-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004565.3(PEX14):c.156C>T(p.Phe52Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,596,574 control chromosomes in the GnomAD database, including 77,544 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5741 hom., cov: 31)

Exomes 𝑓: 0.31 ( 71803 hom. )

Consequence

PEX14
NM_004565.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.38

Variant links:

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]

PEX14 links:

PEX14 (HGNC:):

PEX14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 1-10536284-C-T is Benign according to our data. Variant chr1-10536284-C-T is described in ClinVar as [Benign]. Clinvar id is 259434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-10536284-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX14	NM_004565.3 linkuse as main transcript	c.156C>T	p.Phe52Phe	synonymous_variant	3/9	ENST00000356607.9	NP_004556.1	O75381-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PEX14	ENST00000356607.9 linkuse as main transcript	c.156C>T	p.Phe52Phe	synonymous_variant	3/9	1	NM_004565.3	ENSP00000349016.4	O75381-1
PEX14	ENST00000491661.2 linkuse as main transcript	c.141C>T	p.Phe47Phe	synonymous_variant	3/6	2		ENSP00000465473.1	K7EK59
PEX14	ENST00000472851.1 linkuse as main transcript	n.517C>T		non_coding_transcript_exon_variant	4/4	3
PEX14	ENST00000492696.1 linkuse as main transcript	n.245C>T		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39120

AN:

151842

Hom.:

5742

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.338

Gnomad ASJ

AF:

0.265

Gnomad EAS

AF:

0.208

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.338

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.322

Gnomad OTH

AF:

0.277

GnomAD3 exomes

AF:

0.295

AC:

74030

AN:

251160

Hom.:

11751

AF XY:

0.291

AC XY:

39564

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.412

Gnomad ASJ exome

AF:

0.272

Gnomad EAS exome

AF:

0.212

Gnomad SAS exome

AF:

0.229

Gnomad FIN exome

AF:

0.330

Gnomad NFE exome

AF:

0.313

Gnomad OTH exome

AF:

0.293

GnomAD4 exome

AF:

0.310

AC:

447902

AN:

1444612

Hom.:

71803

Cov.:

AF XY:

0.307

AC XY:

221248

AN XY:

719704

show subpopulations

Gnomad4 AFR exome

AF:

0.0987

Gnomad4 AMR exome

AF:

0.403

Gnomad4 ASJ exome

AF:

0.267

Gnomad4 EAS exome

AF:

0.186

Gnomad4 SAS exome

AF:

0.223

Gnomad4 FIN exome

AF:

0.332

Gnomad4 NFE exome

AF:

0.325

Gnomad4 OTH exome

AF:

0.297

GnomAD4 genome

AF:

0.257

AC:

39111

AN:

151962

Hom.:

5741

Cov.:

AF XY:

0.258

AC XY:

19127

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.107

Gnomad4 AMR

AF:

0.337

Gnomad4 ASJ

AF:

0.265

Gnomad4 EAS

AF:

0.208

Gnomad4 SAS

AF:

0.239

Gnomad4 FIN

AF:

0.338

Gnomad4 NFE

AF:

0.322

Gnomad4 OTH

AF:

0.275

Alfa

AF:

0.298

Hom.:

5010

Bravo

AF:

0.253

Asia WGS

AF:

0.253

AC:

879

AN:

3478

EpiCase

AF:

0.314

EpiControl

AF:

0.318

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 13, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 21, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Peroxisome biogenesis disorder 13A (Zellweger)

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Peroxisome biogenesis disorder, complementation group K

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

-0.35

CADD

Benign

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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