Genetic Variant PEX14:c.170-8951C>T (chr1-10590287-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004565.3(PEX14):c.170-8951C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,190 control chromosomes in the GnomAD database, including 7,433 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 7433 hom., cov: 34)

Consequence

PEX14
NM_004565.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.603

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

peroxisome biogenesis disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
peroxisome biogenesis disorder 13A (Zellweger)
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
Zellweger spectrum disorders
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PEX14 links:

ENSG00000307253 (HGNC:):

ENSG00000307253 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX14	NM_004565.3 link	c.170-8951C>T		intron_variant	Intron 3 of 8	ENST00000356607.9	NP_004556.1	O75381-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PEX14	ENST00000356607.9 link	c.170-8951C>T	intron_variant	Intron 3 of 8	1	NM_004565.3	ENSP00000349016.4	O75381-1
PEX14	ENST00000491661.2 link	c.155-8951C>T	intron_variant	Intron 3 of 5	2		ENSP00000465473.1	K7EK59
ENSG00000307253	ENST00000824750.1 link	n.165-339G>A	intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41497

AN:

152072

Hom.:

7437

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0704

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.263

Gnomad ASJ

AF:

0.421

Gnomad EAS

AF:

0.00288

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.304

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.405

Gnomad OTH

AF:

0.312

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.273

AC:

41484

AN:

152190

Hom.:

7433

Cov.:

AF XY:

0.267

AC XY:

19879

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0702

AC:

2918

AN:

41550

American (AMR)

AF:

0.262

AC:

4008

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.421

AC:

1462

AN:

3472

East Asian (EAS)

AF:

0.00308

AC:

AN:

5188

South Asian (SAS)

AF:

0.243

AC:

1169

AN:

4820

European-Finnish (FIN)

AF:

0.304

AC:

3204

AN:

10554

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.405

AC:

27526

AN:

67990

Other (OTH)

AF:

0.307

AC:

648

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1396

2792

4189

5585

6981

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.374

Hom.:

10491

Bravo

AF:

0.259

Asia WGS

AF:

0.109

AC:

379

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

3.7

(source)

DANN

Benign

0.67

PhyloP100

0.60

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over