rs616402

Positions:

• chr1-10506215-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEX14	NM_004565.3	c.84+10894C>T		intron_variant		ENST00000356607.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX14	ENST00000356607.9	c.84+10894C>T		intron_variant		1	NM_004565.3	P1
PEX14	ENST00000491661.2	c.69+10894C>T		intron_variant		2
PEX14	ENST00000472851.1	n.342-10813C>T		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.312

Alfa AF: 0.315 Hom.: 2182

Bravo AF: 0.301

Asia WGS AF: 0.289 AC: 1009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.89
DANN	Benign	0.21

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

Publications

LitVar

Other links and lift over

dbSNP: rs616402; hg19: chr1-10566272;