11-45913833-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

21 publications found

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 Gene-Disease associations (from GenCC):

peroxisome biogenesis disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
peroxisome biogenesis disorder 8A (Zellweger)
Inheritance: AR Classification: DEFINITIVE, MODERATE Submitted by: G2P, Ambry Genetics
peroxisome biogenesis disorder 8B
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
Zellweger spectrum disorders
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PEX16 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 259547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
PEX16	NM_004813.4 link	c.873T>C	p.Tyr291Tyr	synonymous_variant	Exon 9 of 11	ENST00000378750.10	NP_004804.2	Q9Y5Y5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PEX16	ENST00000378750.10 link	c.873T>C	p.Tyr291Tyr	synonymous_variant	Exon 9 of 11	1	NM_004813.4	ENSP00000368024.5	Q9Y5Y5-1
PEX16	ENST00000241041.7 link	c.873T>C	p.Tyr291Tyr	synonymous_variant	Exon 9 of 11	1		ENSP00000241041.3	Q9Y5Y5-2
PEX16	ENST00000532681.5 link	c.588T>C	p.Tyr196Tyr	synonymous_variant	Exon 9 of 11	3		ENSP00000434654.1	E9PP98
PEX16	ENST00000533151.5 link	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

GnomAD2 exomes

AF:

0.809

AC:

202306

AN:

250204

AF XY:

0.828

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 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

African (AFR)

AF:

0.578

AC:

19338

AN:

33478

American (AMR)

AF:

0.589

AC:

26328

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.870

AC:

22743

AN:

26132

East Asian (EAS)

AF:

0.382

AC:

15160

AN:

39694

South Asian (SAS)

AF:

0.868

AC:

74848

AN:

86252

European-Finnish (FIN)

AF:

0.944

AC:

50155

AN:

53146

Middle Eastern (MID)

AF:

0.871

AC:

5024

AN:

5768

European-Non Finnish (NFE)

AF:

0.925

AC:

1028479

AN:

1111918

Other (OTH)

AF:

0.863

AC:

52102

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

7307

14614

21920

29227

36534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21322

42644

63966

85288

106610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.790

AC:

120226

AN:

152198

Hom.:

49620

Cov.:

AF XY:

0.789

AC XY:

58743

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.590

AC:

24468

AN:

41482

American (AMR)

AF:

0.703

AC:

10761

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.862

AC:

2994

AN:

3472

East Asian (EAS)

AF:

0.432

AC:

2226

AN:

5156

South Asian (SAS)

AF:

0.861

AC:

4157

AN:

4830

European-Finnish (FIN)

AF:

0.948

AC:

10071

AN:

10618

Middle Eastern (MID)

AF:

0.847

AC:

249

AN:

294

European-Non Finnish (NFE)

AF:

0.923

AC:

62757

AN:

68018

Other (OTH)

AF:

0.804

AC:

1697

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1120

2240

3361

4481

5601

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

856

1712

2568

3424

4280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.863

Hom.:

40104

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

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Oct 21, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 13, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Peroxisome biogenesis disorder

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.97

CADD

Benign

0.045

(source)

DANN

Benign

0.17

PhyloP100

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over