chr1-10524615-G-A

Variant names:

• chr1-10524615-G-A
• rs2506887
• NM_004565.3:c.85-11598G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.601
• Publications: 10 publications found

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

ACMG classification

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.

Variant Effect in Transcripts

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

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX14	NM_004565.3	MANE Select	c.85-11598G>A		intron	N/A	NP_004556.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX14	ENST00000356607.9	TSL:1 MANE Select	c.85-11598G>A		intron	N/A	ENSP00000349016.4
	PEX14	ENST00000889280.1		c.85-11598G>A		intron	N/A	ENSP00000559339.1
	PEX14	ENST00000923290.1		c.37-11598G>A		intron	N/A	ENSP00000593349.1

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123180 AN: 152022 Hom.: 50009 Cov.: 31

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

African (AFR) AF: 0.821 AC: 23 AN: 28

American (AMR) AF: 1.00 AC: 8 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 6 AN: 8

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 0.808 AC: 21 AN: 26

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.857 AC: 1010 AN: 1178

Other (OTH) AF: 0.841 AC: 37 AN: 44

GnomAD4 genome AF: 0.810 AC: 123246 AN: 152140 Hom.: 50031 Cov.: 31 AF XY: 0.807 AC XY: 59979 AN XY: 74358

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.25
PhyloP100		0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2506887; hg19: chr1-10584672;