1-10506215-C-T

Variant names:

• chr1-10506215-C-T
• rs616402
• NM_004565.3:c.84+10894C>T

Variant summary

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

The NM_004565.3(PEX14):​c.84+10894C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,044 control chromosomes in the GnomAD database, including 6,718 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 0.29 (6718 hom., cov: 32)
• Consequence: PEX14 NM_004565.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269
• Publications: 12 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.37 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.84+10894C>T		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.84+10894C>T		intron	N/A	ENSP00000349016.4
	PEX14	ENST00000889280.1		c.84+10894C>T		intron	N/A	ENSP00000559339.1
	PEX14	ENST00000923290.1		c.37-29998C>T		intron	N/A	ENSP00000593349.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44748 AN: 151926 Hom.: 6710 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.294 AC: 44768 AN: 152044 Hom.: 6718 Cov.: 32 AF XY: 0.295 AC XY: 21887 AN XY: 74304

African (AFR) AF: 0.237 AC: 9830 AN: 41472

American (AMR) AF: 0.379 AC: 5785 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 938 AN: 3468

East Asian (EAS) AF: 0.324 AC: 1673 AN: 5168

South Asian (SAS) AF: 0.239 AC: 1154 AN: 4820

European-Finnish (FIN) AF: 0.318 AC: 3357 AN: 10554

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 20980 AN: 67972

Other (OTH) AF: 0.312 AC: 659 AN: 2110

Alfa AF: 0.313 Hom.: 3612

Bravo AF: 0.301

Asia WGS AF: 0.289 AC: 1009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.89
DANN	Benign	0.21
PhyloP100		-0.27
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: rs616402; hg19: chr1-10566272;