chr1-10474958-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BP6

The NM_004565.3(PEX14):​c.-9C>T variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00000206 in 1,454,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PEX14
NM_004565.3 5_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.77
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.18).
BP6
Variant 1-10474958-C-T is Benign according to our data. Variant chr1-10474958-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3029435.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PEX14NM_004565.3 linkuse as main transcriptc.-9C>T 5_prime_UTR_variant 1/9 ENST00000356607.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PEX14ENST00000356607.9 linkuse as main transcriptc.-9C>T 5_prime_UTR_variant 1/91 NM_004565.3 P1O75381-1
PEX14ENST00000472851.1 linkuse as main transcriptn.293+2378C>T intron_variant, non_coding_transcript_variant 3
PEX14ENST00000491661.2 linkuse as main transcript upstream_gene_variant 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1454806
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
722996
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

PEX14-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesMay 08, 2023This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.18
CADD
Benign
22
DANN
Benign
0.96

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-10535015; COSMIC: COSV100750304; COSMIC: COSV100750304; API