chr1-10599281-C-G

Position:

chr1-10599281-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004565.3(PEX14):c.213C>G(p.Gly71Gly) variant causes a synonymous change. The variant allele was found at a frequency of 0.0153 in 1,613,366 control chromosomes in the GnomAD database, including 294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0097 ( 24 hom., cov: 33)

Exomes 𝑓: 0.016 ( 270 hom. )

Consequence

PEX14
NM_004565.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.21

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]

PEX14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 1-10599281-C-G is Benign according to our data. Variant chr1-10599281-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 259435.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00968 (1474/152324) while in subpopulation NFE AF= 0.0159 (1084/68036). AF 95% confidence interval is 0.0151. There are 24 homozygotes in gnomad4. There are 668 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX14	NM_004565.3 linkuse as main transcript	c.213C>G	p.Gly71Gly	synonymous_variant	4/9	ENST00000356607.9	NP_004556.1	O75381-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX14	ENST00000356607.9 linkuse as main transcript	c.213C>G	p.Gly71Gly	synonymous_variant	4/9	1	NM_004565.3	ENSP00000349016.4		O75381-1
PEX14	ENST00000491661.2 linkuse as main transcript	c.198C>G	p.Gly66Gly	synonymous_variant	4/6	2		ENSP00000465473.1		K7EK59

Frequencies

GnomAD3 genomes

AF:

0.00968

AC:

1474

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0116

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00433

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0159

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00899

AC:

2260

AN:

251444

Hom.:

AF XY:

0.00918

AC XY:

1247

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00314

Gnomad AMR exome

AF:

0.00682

Gnomad ASJ exome

AF:

0.00774

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00508

Gnomad NFE exome

AF:

0.0151

Gnomad OTH exome

AF:

0.00945

GnomAD4 exome

AF:

0.0159

AC:

23175

AN:

1461042

Hom.:

270

Cov.:

AF XY:

0.0152

AC XY:

11060

AN XY:

726872

show subpopulations

Gnomad4 AFR exome

AF:

0.00296

Gnomad4 AMR exome

AF:

0.00678

Gnomad4 ASJ exome

AF:

0.00872

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.00584

Gnomad4 NFE exome

AF:

0.0192

Gnomad4 OTH exome

AF:

0.0144

GnomAD4 genome

AF:

0.00968

AC:

1474

AN:

152324

Hom.:

Cov.:

AF XY:

0.00897

AC XY:

668

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00265

Gnomad4 AMR

AF:

0.0116

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00433

Gnomad4 NFE

AF:

0.0159

Gnomad4 OTH

AF:

0.00994

Alfa

AF:

0.0101

Hom.:

Bravo

AF:

0.0103

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0164

EpiControl

AF:

0.0155

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Jan 04, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Peroxisome biogenesis disorder 13A (Zellweger)

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 28, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Peroxisome biogenesis disorder, complementation group K

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over