1-10506158-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX14	NM_004565.3	c.84+10837A>G		intron_variant	Intron 2 of 8	ENST00000356607.9	NP_004556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX14	ENST00000356607.9	c.84+10837A>G		intron_variant	Intron 2 of 8	1	NM_004565.3	ENSP00000349016.4
PEX14	ENST00000491661.2	c.69+10837A>G		intron_variant	Intron 2 of 5	2		ENSP00000465473.1
PEX14	ENST00000472851.1	n.341+10837A>G		intron_variant	Intron 2 of 3	3

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

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.291

Alfa AF: 0.321 Hom.: 11753

Bravo AF: 0.276

Asia WGS AF: 0.286 AC: 995 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Peroxisome biogenesis disorder, complementation group K Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.3
DANN	Benign	0.55

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: rs616488; hg19: chr1-10566215;