1-10506158-A-G

Variant names:

• chr1-10506158-A-G
• rs616488
• NM_004565.3:c.84+10837A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004565.3(PEX14):​c.84+10837A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,076 control chromosomes in the GnomAD database, including 6,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (6474 hom., cov: 33)
• Consequence: PEX14 NM_004565.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.136
• Publications: 91 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-10506158-A-G is Benign according to our data. Variant chr1-10506158-A-G is described in ClinVar as Benign. ClinVar VariationId is 225769.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.364 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.84+10837A>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.84+10837A>G		intron	N/A	ENSP00000349016.4	O75381-1
	PEX14	ENST00000889280.1		c.84+10837A>G		intron	N/A	ENSP00000559339.1
	PEX14	ENST00000923290.1		c.37-30055A>G		intron	N/A	ENSP00000593349.1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41694 AN: 151958 Hom.: 6472 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.274 AC: 41696 AN: 152076 Hom.: 6474 Cov.: 33 AF XY: 0.274 AC XY: 20389 AN XY: 74336

African (AFR) AF: 0.124 AC: 5144 AN: 41512

American (AMR) AF: 0.373 AC: 5689 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 962 AN: 3468

East Asian (EAS) AF: 0.326 AC: 1686 AN: 5172

South Asian (SAS) AF: 0.241 AC: 1163 AN: 4820

European-Finnish (FIN) AF: 0.336 AC: 3550 AN: 10574

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22471 AN: 67946

Other (OTH) AF: 0.291 AC: 614 AN: 2110

Alfa AF: 0.313 Hom.: 27327

Bravo AF: 0.276

Asia WGS AF: 0.286 AC: 995 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Peroxisome biogenesis disorder, complementation group K (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.3
DANN	Benign	0.55
PhyloP100		0.14
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: rs616488; hg19: chr1-10566215;