2-61017528-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000444100.2(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 ENST00000444100.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.30

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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/exons	MANE	UniProt
PUS10	NM_144709.4	c.-16+480T>G		intron_variant		ENST00000316752.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX13	ENST00000444100.2	c.-232A>C		5_prime_UTR_variant	1/2	1
PUS10	ENST00000316752.11	c.-16+480T>G		intron_variant		1	NM_144709.4	P1
PUS10	ENST00000602599.1	n.252+480T>G		intron_variant, non_coding_transcript_variant		1
PEX13	ENST00000401576.1			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35351 AN: 152056 Hom.: 5075 Cov.: 32

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.: 0 AF XY: 0.155 AC XY: 29150 AN XY: 187556

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.: 32 AF XY: 0.231 AC XY: 17173 AN XY: 74408

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 07, 2018

- -

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

Other links and lift over

dbSNP: rs12988616; hg19: chr2-61244663;