rs284238

Variant names:

• chr1-10618431-A-T
• rs284238
• NM_004565.3:c.384+14A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004565.3(PEX14):​c.384+14A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,599,916 control chromosomes in the GnomAD database, including 18,358 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3289 hom., cov: 33)
  • Exomes 𝑓: 0.14 (15069 hom.)
• Consequence: PEX14 NM_004565.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.520
• 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: 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-10618431-A-T is Benign according to our data. Variant chr1-10618431-A-T is described in ClinVar as Benign. ClinVar VariationId is 95145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 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.384+14A>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.384+14A>T		intron	N/A	ENSP00000349016.4
	PEX14	ENST00000491661.2	TSL:2	c.369+14A>T		intron	N/A	ENSP00000465473.1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28931 AN: 152152 Hom.: 3269 Cov.: 33

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.0778

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.179

GnomAD2 exomes AF: 0.155 AC: 38508 AN: 248840 AF XY: 0.157

Gnomad AFR exome AF: 0.311

Gnomad AMR exome AF: 0.104

Gnomad ASJ exome AF: 0.187

Gnomad EAS exome AF: 0.0889

Gnomad FIN exome AF: 0.235

Gnomad NFE exome AF: 0.130

Gnomad OTH exome AF: 0.151

GnomAD4 exome AF: 0.137 AC: 198517 AN: 1447646 Hom.: 15069 Cov.: 28 AF XY: 0.139 AC XY: 100463 AN XY: 721146

African (AFR) AF: 0.323 AC: 10690 AN: 33134

American (AMR) AF: 0.109 AC: 4885 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 4799 AN: 26068

East Asian (EAS) AF: 0.0726 AC: 2879 AN: 39630

South Asian (SAS) AF: 0.195 AC: 16806 AN: 86018

European-Finnish (FIN) AF: 0.233 AC: 12095 AN: 51936

Middle Eastern (MID) AF: 0.168 AC: 967 AN: 5750

European-Non Finnish (NFE) AF: 0.124 AC: 136480 AN: 1100456

Other (OTH) AF: 0.149 AC: 8916 AN: 59974

GnomAD4 genome AF: 0.190 AC: 28992 AN: 152270 Hom.: 3289 Cov.: 33 AF XY: 0.196 AC XY: 14596 AN XY: 74466

African (AFR) AF: 0.308 AC: 12820 AN: 41566

American (AMR) AF: 0.146 AC: 2237 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 664 AN: 3468

East Asian (EAS) AF: 0.0778 AC: 403 AN: 5182

South Asian (SAS) AF: 0.186 AC: 899 AN: 4830

European-Finnish (FIN) AF: 0.245 AC: 2597 AN: 10600

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8777 AN: 68000

Other (OTH) AF: 0.177 AC: 373 AN: 2110

Alfa AF: 0.158 Hom.: 407

Bravo AF: 0.185

Asia WGS AF: 0.129 AC: 452 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Peroxisome biogenesis disorder 13A (Zellweger) (1)
-	-	1	Peroxisome biogenesis disorder, complementation group K (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.14
DANN	Benign	0.56
PhyloP100		-0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs284238; hg19: chr1-10678488; COSMIC: COSV63061569; COSMIC: COSV63061569;