NM_004565.3:c.84+10894C>T

Variant names:

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019): 0P and 12B. BA1BP4_Strong

The NM_004565.3(PEX14):c.84+10894C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.294 (AC=44,768) in the gnomAD database across 152,044 control chromosomes, including 6,718 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.37. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 6718 hom., cov: 32)

Consequence

PEX14
NM_004565.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.269

Publications

12 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, PanelApp Australia, Labcorp Genetics (formerly Invitae)
Zellweger spectrum disorders
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PEX14 links:

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new If you want to explore the variant's impact on the transcript NM_004565.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

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

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.3705 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_004565.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX14	NM_004565.3	MANE Select	c.84+10894C>T		intron	N/A	NP_004556.1	O75381-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PEX14	ENST00000356607.9	TSL:1 MANE Select	c.84+10894C>T	intron	N/A	ENSP00000349016.4	O75381-1
PEX14	ENST00000889280.1		c.84+10894C>T	intron	N/A	ENSP00000559339.1
PEX14	ENST00000923290.1		c.37-29998C>T	intron	N/A	ENSP00000593349.1

Frequencies

GnomAD3 genomes

AF:

0.295

AC:

44748

AN:

151926

Hom.:

6710

Cov.:

show subpopulations

Gnomad AFR

AF:

0.237

Gnomad AMI

AF:

0.354

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.270

Gnomad EAS

AF:

0.324

Gnomad SAS

AF:

0.241

Gnomad FIN

AF:

0.318

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.309

Gnomad OTH

AF:

0.315

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

GnomAD4 genome

AF:

0.294

AC:

44768

AN:

152044

Hom.:

6718

Cov.:

AF XY:

0.295

AC XY:

21887

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.237

AC:

9830

AN:

41472

American (AMR)

AF:

0.379

AC:

5785

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.270

AC:

938

AN:

3468

East Asian (EAS)

AF:

0.324

AC:

1673

AN:

5168

South Asian (SAS)

AF:

0.239

AC:

1154

AN:

4820

European-Finnish (FIN)

AF:

0.318

AC:

3357

AN:

10554

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.309

AC:

20980

AN:

67972

Other (OTH)

AF:

0.312

AC:

659

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1625

3249

4874

6498

8123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

456

912

1368

1824

2280

<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:

0.313

Hom.:

3612

Bravo

AF:

0.301

Asia WGS

AF:

0.289

AC:

1009

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.286

AC:

35078

AN:

122519

Turkish Variome

AF:

0.228

AC:

353

AN:

1546

Hom.:

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.334

AC:

2991

AN:

8960

Hom.:

489

ABraOM SABE-WGS-1171

AF:

0.302

AC:

708

AN:

2342

Hom.:

108

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.89

(source)

DANN

Benign

0.21

PhyloP100

-0.27

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over