Genetic Variant PEX13:c.-232A>C (chr2-61017528-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000444100(PEX13):c.-232A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 512,166 control chromosomes in the GnomAD database, including 10,994 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5077 hom., cov: 32)

Exomes 𝑓: 0.16 ( 5917 hom. )

Consequence

PEX13
ENST00000444100 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.30

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:

PUS10 (HGNC:26505): (pseudouridine synthase 10) Pseudouridination, the isomerization of uridine to pseudouridine, is the most common posttranscriptional nucleotide modification found in RNA and is essential for biologic functions such as spliceosome biogenesis. Pseudouridylate synthases, such as PUS10, catalyze pseudouridination of structural RNAs, including transfer, ribosomal, and splicing RNAs. These enzymes also act as RNA chaperones, facilitating the correct folding and assembly of tRNAs (McCleverty et al., 2007 [PubMed 17900615]).[supplied by OMIM, May 2009]

PUS10 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=-0.84).

BP6

Variant 2-61017528-A-C is Benign according to our data. Variant chr2-61017528-A-C is described in ClinVar as [Benign]. Clinvar id is 1289711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PUS10	NM_144709.4 link	c.-16+480T>G		intron_variant	Intron 1 of 17	ENST00000316752.11	NP_653310.2	Q3MIT2
PEX13	NM_002618.4 link	c.-232A>C		upstream_gene_variant		ENST00000295030.6	NP_002609.1	Q92968

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PUS10	ENST00000316752.11 link	c.-16+480T>G		intron_variant	Intron 1 of 17	1	NM_144709.4	ENSP00000326003.6		Q3MIT2
PEX13	ENST00000295030.6 link	c.-232A>C		upstream_gene_variant		1	NM_002618.4	ENSP00000295030.4		Q92968

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35351

AN:

152056

Hom.:

5075

Cov.:

show subpopulations

Gnomad AFR

AF:

0.394

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.0914

Gnomad EAS

AF:

0.0264

Gnomad SAS

AF:

0.0468

Gnomad FIN

AF:

0.231

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.189

Gnomad OTH

AF:

0.200

GnomAD4 exome

AF:

0.163

AC:

58595

AN:

359992

Hom.:

5917

Cov.:

AF XY:

0.155

AC XY:

29150

AN XY:

187556

show subpopulations

Gnomad4 AFR exome

AF:

0.397

Gnomad4 AMR exome

AF:

0.132

Gnomad4 ASJ exome

AF:

0.0875

Gnomad4 EAS exome

AF:

0.0221

Gnomad4 SAS exome

AF:

0.0524

Gnomad4 FIN exome

AF:

0.234

Gnomad4 NFE exome

AF:

0.183

Gnomad4 OTH exome

AF:

0.170

GnomAD4 genome

AF:

0.232

AC:

35371

AN:

152174

Hom.:

5077

Cov.:

AF XY:

0.231

AC XY:

17173

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.394

Gnomad4 AMR

AF:

0.161

Gnomad4 ASJ

AF:

0.0914

Gnomad4 EAS

AF:

0.0266

Gnomad4 SAS

AF:

0.0466

Gnomad4 FIN

AF:

0.231

Gnomad4 NFE

AF:

0.189

Gnomad4 OTH

AF:

0.199

Alfa

AF:

0.182

Hom.:

5455

Bravo

AF:

0.234

Asia WGS

AF:

0.0800

AC:

276

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.59

DANN

Benign

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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