1-10553503-A-G

Variant names:

• chr1-10553503-A-G
• rs10864463
• NM_004565.3:c.169+17206A>G

Variant summary

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

The NM_004565.3(PEX14):​c.169+17206A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 152,108 control chromosomes in the GnomAD database, including 41,424 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 0.73 (41424 hom., cov: 31)
• Consequence: PEX14 NM_004565.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.760
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.813 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.169+17206A>G		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.169+17206A>G		intron	N/A	ENSP00000349016.4
	PEX14	ENST00000491661.2	TSL:2	c.154+17206A>G		intron	N/A	ENSP00000465473.1

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110661 AN: 151990 Hom.: 41415 Cov.: 31

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.743

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

GnomAD4 genome AF: 0.728 AC: 110711 AN: 152108 Hom.: 41424 Cov.: 31 AF XY: 0.726 AC XY: 54000 AN XY: 74360

African (AFR) AF: 0.550 AC: 22798 AN: 41478

American (AMR) AF: 0.775 AC: 11844 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2763 AN: 3470

East Asian (EAS) AF: 0.665 AC: 3431 AN: 5162

South Asian (SAS) AF: 0.670 AC: 3227 AN: 4818

European-Finnish (FIN) AF: 0.808 AC: 8551 AN: 10586

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.819 AC: 55680 AN: 67992

Other (OTH) AF: 0.739 AC: 1562 AN: 2114

Alfa AF: 0.765 Hom.: 46921

Bravo AF: 0.720

Asia WGS AF: 0.676 AC: 2350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.37
DANN	Benign	0.24
PhyloP100		-0.76
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: rs10864463; hg19: chr1-10613560;