chr1-10612878-A-G

Variant names:

• chr1-10612878-A-G
• rs481453
• NM_004565.3:c.299-5454A>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.299-5454A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,208 control chromosomes in the GnomAD database, including 4,470 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 0.21 (4470 hom., cov: 33)
• Consequence: PEX14 NM_004565.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435
• Publications: 7 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• Zellweger spectrum disorders

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000287727 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.391 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX14	NM_004565.3	MANE Select	c.299-5454A>G		intron	N/A	NP_004556.1	O75381-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX14	ENST00000356607.9	TSL:1 MANE Select	c.299-5454A>G		intron	N/A	ENSP00000349016.4	O75381-1
	PEX14	ENST00000889280.1		c.299-5454A>G		intron	N/A	ENSP00000559339.1
	PEX14	ENST00000923290.1		c.251-5454A>G		intron	N/A	ENSP00000593349.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32255 AN: 152090 Hom.: 4458 Cov.: 33

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.212 AC: 32308 AN: 152208 Hom.: 4470 Cov.: 33 AF XY: 0.213 AC XY: 15886 AN XY: 74420

African (AFR) AF: 0.396 AC: 16441 AN: 41532

American (AMR) AF: 0.146 AC: 2234 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 702 AN: 3470

East Asian (EAS) AF: 0.122 AC: 628 AN: 5168

South Asian (SAS) AF: 0.194 AC: 937 AN: 4826

European-Finnish (FIN) AF: 0.178 AC: 1884 AN: 10606

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8857 AN: 67986

Other (OTH) AF: 0.196 AC: 415 AN: 2112

Alfa AF: 0.157 Hom.: 3476

Bravo AF: 0.214

Asia WGS AF: 0.151 AC: 526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.6
DANN	Benign	0.37
PhyloP100		0.43
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: rs481453; hg19: chr1-10672935;