Genetic Variant NM_004565.3:c.85-11598G>A (chr1-10524615-G-A) – 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.85-11598G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 153,436 control chromosomes in the GnomAD database, including 50,506 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 0.81 ( 50031 hom., cov: 31)

Exomes 𝑓: 0.86 ( 475 hom. )

Consequence

PEX14
NM_004565.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.601

Publications

10 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:

Genome browser will be placed here

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=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX14	NM_004565.3 link	c.85-11598G>A		intron_variant	Intron 2 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.85-11598G>A	intron_variant	Intron 2 of 8	1	NM_004565.3	ENSP00000349016.4	O75381-1
PEX14	ENST00000491661.2 link	c.70-11598G>A	intron_variant	Intron 2 of 5	2		ENSP00000465473.1	K7EK59
PEX14	ENST00000472851.1 link	n.445+7484G>A	intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.810

AC:

123180

AN:

152022

Hom.:

50009

Cov.:

show subpopulations

Gnomad AFR

AF:

0.774

Gnomad AMI

AF:

0.752

Gnomad AMR

AF:

0.821

Gnomad ASJ

AF:

0.807

Gnomad EAS

AF:

0.793

Gnomad SAS

AF:

0.702

Gnomad FIN

AF:

0.847

Gnomad MID

AF:

0.734

Gnomad NFE

AF:

0.835

Gnomad OTH

AF:

0.805

GnomAD4 exome

AF:

0.856

AC:

1109

AN:

1296

Hom.:

475

AF XY:

0.845

AC XY:

558

AN XY:

660

show subpopulations

African (AFR)

AF:

0.821

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.808

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.857

AC:

1010

AN:

1178

Other (OTH)

AF:

0.841

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.810

AC:

123246

AN:

152140

Hom.:

50031

Cov.:

AF XY:

0.807

AC XY:

59979

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.773

AC:

32068

AN:

41462

American (AMR)

AF:

0.821

AC:

12553

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.807

AC:

2802

AN:

3472

East Asian (EAS)

AF:

0.794

AC:

4110

AN:

5178

South Asian (SAS)

AF:

0.702

AC:

3381

AN:

4816

European-Finnish (FIN)

AF:

0.847

AC:

8965

AN:

10586

Middle Eastern (MID)

AF:

0.735

AC:

216

AN:

294

European-Non Finnish (NFE)

AF:

0.835

AC:

56771

AN:

68014

Other (OTH)

AF:

0.804

AC:

1694

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1183

2366

3549

4732

5915

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

880

1760

2640

3520

4400

<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:

0.818

Hom.:

27265

Bravo

AF:

0.810

Asia WGS

AF:

0.737

AC:

2563

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.2

(source)

DANN

Benign

0.25

PhyloP100

0.60

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over