chr1-10590287-C-T

Position:

• chr1-10590287-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.170-8951C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,190 control chromosomes in the GnomAD database, including 7,433 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 0.27 (7433 hom., cov: 34)
• Consequence: PEX14 NM_004565.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.603

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEX14	NM_004565.3	c.170-8951C>T		intron_variant		ENST00000356607.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX14	ENST00000356607.9	c.170-8951C>T		intron_variant		1	NM_004565.3	P1
PEX14	ENST00000491661.2	c.155-8951C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41497 AN: 152072 Hom.: 7437 Cov.: 34

Gnomad AFR AF: 0.0704

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.00288

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.273 AC: 41484 AN: 152190 Hom.: 7433 Cov.: 34 AF XY: 0.267 AC XY: 19879 AN XY: 74390

Gnomad4 AFR AF: 0.0702

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.421

Gnomad4 EAS AF: 0.00308

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.307

Alfa AF: 0.368 Hom.: 7494

Bravo AF: 0.259

Asia WGS AF: 0.109 AC: 379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.7
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11577757; hg19: chr1-10650344;