Variant 11-45914484-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000378750.10(PEX16):c.542-16C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 1,608,200 control chromosomes in the GnomAD database, including 621,438 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.79 ( 49021 hom., cov: 34)

Exomes 𝑓: 0.88 ( 572417 hom. )

Consequence

PEX16
ENST00000378750.10 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.834

Variant links:

Genes affected

PEX16 (HGNC:8857): (peroxisomal biogenesis factor 16) The protein encoded by this gene is an integral peroxisomal membrane protein. An inactivating nonsense mutation localized to this gene was observed in a patient with Zellweger syndrome of the complementation group CGD/CG9. Expression of this gene product morphologically and biochemically restores the formation of new peroxisomes, suggesting a role in peroxisome organization and biogenesis. Alternative splicing has been observed for this gene and two variants have been described. [provided by RefSeq, Jul 2008]

PEX16 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=-0.85).

BP6

Variant 11-45914484-G-A is Benign according to our data. Variant chr11-45914484-G-A is described in ClinVar as [Benign]. Clinvar id is 259546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-45914484-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX16	NM_004813.4 linkuse as main transcript	c.542-16C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000378750.10	NP_004804.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX16	ENST00000378750.10 linkuse as main transcript	c.542-16C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004813.4	ENSP00000368024	P1	Q9Y5Y5-1

Frequencies

GnomAD3 genomes

AF:

0.786

AC:

119480

AN:

152028

Hom.:

49004

Cov.:

show subpopulations

Gnomad AFR

AF:

0.587

Gnomad AMI

AF:

0.927

Gnomad AMR

AF:

0.702

Gnomad ASJ

AF:

0.852

Gnomad EAS

AF:

0.434

Gnomad SAS

AF:

0.855

Gnomad FIN

AF:

0.945

Gnomad MID

AF:

0.845

Gnomad NFE

AF:

0.916

Gnomad OTH

AF:

0.797

GnomAD3 exomes

AF:

0.801

AC:

197084

AN:

246036

Hom.:

82741

AF XY:

0.821

AC XY:

109569

AN XY:

133534

show subpopulations

Gnomad AFR exome

AF:

0.587

Gnomad AMR exome

AF:

0.572

Gnomad ASJ exome

AF:

0.860

Gnomad EAS exome

AF:

0.441

Gnomad SAS exome

AF:

0.860

Gnomad FIN exome

AF:

0.940

Gnomad NFE exome

AF:

0.914

Gnomad OTH exome

AF:

0.845

GnomAD4 exome

AF:

0.879

AC:

1279385

AN:

1456054

Hom.:

572417

Cov.:

AF XY:

0.880

AC XY:

637714

AN XY:

724562

show subpopulations

Gnomad4 AFR exome

AF:

0.574

Gnomad4 AMR exome

AF:

0.586

Gnomad4 ASJ exome

AF:

0.859

Gnomad4 EAS exome

AF:

0.381

Gnomad4 SAS exome

AF:

0.858

Gnomad4 FIN exome

AF:

0.937

Gnomad4 NFE exome

AF:

0.918

Gnomad4 OTH exome

AF:

0.855

GnomAD4 genome

AF:

0.786

AC:

119539

AN:

152146

Hom.:

49021

Cov.:

AF XY:

0.785

AC XY:

58415

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.588

Gnomad4 AMR

AF:

0.701

Gnomad4 ASJ

AF:

0.852

Gnomad4 EAS

AF:

0.434

Gnomad4 SAS

AF:

0.854

Gnomad4 FIN

AF:

0.945

Gnomad4 NFE

AF:

0.916

Gnomad4 OTH

AF:

0.800

Alfa

AF:

0.816

Hom.:

12275

Bravo

AF:

0.753

Asia WGS

AF:

0.703

AC:

2446

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 07, 2018	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 21, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Peroxisome biogenesis disorder 8B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Peroxisome biogenesis disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Peroxisome biogenesis disorder 8A (Zellweger)

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.025

DANN

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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