chr1-10546939-G-T

Variant names:

• chr1-10546939-G-T
• rs2480775
• NM_004565.3:c.169+10642G>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.169+10642G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 152,000 control chromosomes in the GnomAD database, including 39,770 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 0.71 (39770 hom., cov: 31)
• Consequence: PEX14 NM_004565.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373
• 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: Ambry Genetics, G2P, 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 (NFE) allele frequency at 95% confidence interval = 0.814 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.169+10642G>T		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.169+10642G>T		intron	N/A	ENSP00000349016.4	O75381-1
	PEX14	ENST00000889280.1		c.169+10642G>T		intron	N/A	ENSP00000559339.1
	PEX14	ENST00000923290.1		c.121+10642G>T		intron	N/A	ENSP00000593349.1

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107486 AN: 151882 Hom.: 39766 Cov.: 31

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.707 AC: 107523 AN: 152000 Hom.: 39770 Cov.: 31 AF XY: 0.707 AC XY: 52488 AN XY: 74284

African (AFR) AF: 0.476 AC: 19723 AN: 41392

American (AMR) AF: 0.767 AC: 11720 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 2764 AN: 3470

East Asian (EAS) AF: 0.665 AC: 3439 AN: 5174

South Asian (SAS) AF: 0.669 AC: 3228 AN: 4822

European-Finnish (FIN) AF: 0.807 AC: 8540 AN: 10580

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.820 AC: 55730 AN: 67972

Other (OTH) AF: 0.722 AC: 1527 AN: 2114

Alfa AF: 0.786 Hom.: 34082

Bravo AF: 0.697

Asia WGS AF: 0.665 AC: 2313 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	0.35
DANN	Benign	0.61
PhyloP100		-0.37
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: rs2480775; hg19: chr1-10606996;