2-61048636-C-G

Position:

chr2-61048636-C-G

Variant summary

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

The NM_002618.4(PEX13):c.1078C>G(p.Leu360Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0337 in 1,614,022 control chromosomes in the GnomAD database, including 1,104 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 72 hom., cov: 33)

Exomes 𝑓: 0.035 ( 1032 hom. )

Consequence

PEX13
NM_002618.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.626

Variant links:

Genes affected

PEX13 (HGNC:8855): (peroxisomal biogenesis factor 13) This gene encodes a peroxisomal membrane protein that binds the type 1 peroxisomal targeting signal receptor via a SH3 domain located in the cytoplasm. Mutations and deficiencies in peroxisomal protein importing and peroxisome assembly lead to peroxisomal biogenesis disorders, an example of which is Zellweger syndrome. [provided by RefSeq, Oct 2008]

PEX13 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 (MetaRNN=0.0025173426).

BP6

Variant 2-61048636-C-G is Benign according to our data. Variant chr2-61048636-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 336670.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 = 0.0238 (3630/152278) while in subpopulation NFE AF= 0.0386 (2627/68022). AF 95% confidence interval is 0.0374. There are 72 homozygotes in gnomad4. There are 1716 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 72 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX13	NM_002618.4 linkuse as main transcript	c.1078C>G	p.Leu360Val	missense_variant	4/4	ENST00000295030.6	NP_002609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX13	ENST00000295030.6 linkuse as main transcript	c.1078C>G	p.Leu360Val	missense_variant	4/4	1	NM_002618.4	ENSP00000295030	P1

Frequencies

GnomAD3 genomes

AF:

0.0238

AC:

3627

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00736

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0181

Gnomad ASJ

AF:

0.00779

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00766

Gnomad FIN

AF:

0.0266

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0386

Gnomad OTH

AF:

0.0282

GnomAD3 exomes

AF:

0.0239

AC:

5998

AN:

251474

Hom.:

118

AF XY:

0.0239

AC XY:

3249

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00658

Gnomad AMR exome

AF:

0.0129

Gnomad ASJ exome

AF:

0.00794

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00866

Gnomad FIN exome

AF:

0.0276

Gnomad NFE exome

AF:

0.0382

Gnomad OTH exome

AF:

0.0259

GnomAD4 exome

AF:

0.0347

AC:

50785

AN:

1461744

Hom.:

1032

Cov.:

AF XY:

0.0341

AC XY:

24797

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.00520

Gnomad4 AMR exome

AF:

0.0132

Gnomad4 ASJ exome

AF:

0.00819

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00926

Gnomad4 FIN exome

AF:

0.0300

Gnomad4 NFE exome

AF:

0.0409

Gnomad4 OTH exome

AF:

0.0297

GnomAD4 genome

AF:

0.0238

AC:

3630

AN:

152278

Hom.:

Cov.:

AF XY:

0.0230

AC XY:

1716

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00734

Gnomad4 AMR

AF:

0.0181

Gnomad4 ASJ

AF:

0.00779

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00849

Gnomad4 FIN

AF:

0.0266

Gnomad4 NFE

AF:

0.0386

Gnomad4 OTH

AF:

0.0279

Alfa

AF:

0.0340

Hom.:

Bravo

AF:

0.0225

TwinsUK

AF:

0.0429

AC:

159

ALSPAC

AF:

0.0462

AC:

178

ESP6500AA

AF:

0.00704

AC:

ESP6500EA

AF:

0.0379

AC:

326

ExAC

AF:

0.0241

AC:

2922

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.0344

EpiControl

AF:

0.0371

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 27, 2023	See Variant Classification Assertion Criteria. -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Peroxisome biogenesis disorder 11A (Zellweger)

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.60

CADD

Benign

5.3

DANN

Benign

0.049

DEOGEN2

Benign

0.31

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.63

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.21

REVEL

Benign

0.15

Sift

Benign

0.47

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.030

MPC

0.085

ClinPred

0.000071

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.025

gMVP

0.19

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