chr1-10521601-G-A

Variant names:

• chr1-10521601-G-A
• rs2056417
• NM_004565.3:c.85-14612G>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.85-14612G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,086 control chromosomes in the GnomAD database, including 5,418 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 0.25 (5418 hom., cov: 32)
• Consequence: PEX14 NM_004565.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199
• Publications: 20 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX14	NM_004565.3	c.85-14612G>A		intron_variant	Intron 2 of 8	ENST00000356607.9	NP_004556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX14	ENST00000356607.9	c.85-14612G>A		intron_variant	Intron 2 of 8	1	NM_004565.3	ENSP00000349016.4
PEX14	ENST00000491661.2	c.70-14612G>A		intron_variant	Intron 2 of 5	2		ENSP00000465473.1
PEX14	ENST00000472851.1	n.445+4470G>A		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38234 AN: 151966 Hom.: 5419 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.251 AC: 38229 AN: 152086 Hom.: 5418 Cov.: 32 AF XY: 0.251 AC XY: 18682 AN XY: 74336

African (AFR) AF: 0.114 AC: 4726 AN: 41516

American (AMR) AF: 0.332 AC: 5071 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 945 AN: 3466

East Asian (EAS) AF: 0.205 AC: 1065 AN: 5184

South Asian (SAS) AF: 0.235 AC: 1134 AN: 4822

European-Finnish (FIN) AF: 0.318 AC: 3357 AN: 10550

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.309 AC: 20963 AN: 67948

Other (OTH) AF: 0.272 AC: 575 AN: 2114

Alfa AF: 0.292 Hom.: 28852

Bravo AF: 0.249

Asia WGS AF: 0.251 AC: 873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.72
PhyloP100		0.20
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: rs2056417; hg19: chr1-10581658;