11-45913833-A-G

Position:

chr11-45913833-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004813.4(PEX16):c.873T>C(p.Tyr291Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 1,613,690 control chromosomes in the GnomAD database, including 633,190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.79 ( 49620 hom., cov: 33)

Exomes 𝑓: 0.89 ( 583570 hom. )

Consequence

PEX16
NM_004813.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.24

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 11-45913833-A-G is Benign according to our data. Variant chr11-45913833-A-G is described in ClinVar as [Benign]. Clinvar id is 259547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-45913833-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.917 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.873T>C	p.Tyr291Tyr	synonymous_variant	9/11	ENST00000378750.10	NP_004804.2	Q9Y5Y5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PEX16	ENST00000378750.10 linkuse as main transcript	c.873T>C	p.Tyr291Tyr	synonymous_variant	9/11	1	NM_004813.4	ENSP00000368024.5	Q9Y5Y5-1
PEX16	ENST00000241041.7 linkuse as main transcript	c.873T>C	p.Tyr291Tyr	synonymous_variant	9/11	1		ENSP00000241041.3	Q9Y5Y5-2
PEX16	ENST00000532681.5 linkuse as main transcript	c.588T>C	p.Tyr196Tyr	synonymous_variant	9/11	3		ENSP00000434654.1	E9PP98
PEX16	ENST00000533151.5 linkuse as main transcript	c.*12T>C		downstream_gene_variant		3		ENSP00000433045.1	E9PMM3

Frequencies

GnomAD3 genomes

AF:

0.790

AC:

120168

AN:

152080

Hom.:

49604

Cov.:

show subpopulations

Gnomad AFR

AF:

0.589

Gnomad AMI

AF:

0.928

Gnomad AMR

AF:

0.704

Gnomad ASJ

AF:

0.862

Gnomad EAS

AF:

0.433

Gnomad SAS

AF:

0.863

Gnomad FIN

AF:

0.948

Gnomad MID

AF:

0.851

Gnomad NFE

AF:

0.923

Gnomad OTH

AF:

0.800

GnomAD3 exomes

AF:

0.809

AC:

202306

AN:

250204

Hom.:

85732

AF XY:

0.828

AC XY:

112163

AN XY:

135496

show subpopulations

Gnomad AFR exome

AF:

0.590

Gnomad AMR exome

AF:

0.575

Gnomad ASJ exome

AF:

0.871

Gnomad EAS exome

AF:

0.441

Gnomad SAS exome

AF:

0.870

Gnomad FIN exome

AF:

0.945

Gnomad NFE exome

AF:

0.921

Gnomad OTH exome

AF:

0.851

GnomAD4 exome

AF:

0.886

AC:

1294177

AN:

1461492

Hom.:

583570

Cov.:

AF XY:

0.887

AC XY:

644946

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.578

Gnomad4 AMR exome

AF:

0.589

Gnomad4 ASJ exome

AF:

0.870

Gnomad4 EAS exome

AF:

0.382

Gnomad4 SAS exome

AF:

0.868

Gnomad4 FIN exome

AF:

0.944

Gnomad4 NFE exome

AF:

0.925

Gnomad4 OTH exome

AF:

0.863

GnomAD4 genome

AF:

0.790

AC:

120226

AN:

152198

Hom.:

49620

Cov.:

AF XY:

0.789

AC XY:

58743

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.590

Gnomad4 AMR

AF:

0.703

Gnomad4 ASJ

AF:

0.862

Gnomad4 EAS

AF:

0.432

Gnomad4 SAS

AF:

0.861

Gnomad4 FIN

AF:

0.948

Gnomad4 NFE

AF:

0.923

Gnomad4 OTH

AF:

0.804

Alfa

AF:

0.878

Hom.:

31533

Bravo

AF:

0.758

Asia WGS

AF:

0.707

AC:

2459

AN:

3478

EpiCase

AF:

0.923

EpiControl

AF:

0.919

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 21, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 13, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Peroxisome biogenesis disorder 8A (Zellweger)

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
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. -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.045

DANN

Benign

0.17

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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