rs3802758

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004813.4(PEX16):c.542-16C>T variant causes a 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
NM_004813.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.834

Publications

23 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 -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 VariationId is 259546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
PEX16	NM_004813.4 link	c.542-16C>T		intron_variant	Intron 6 of 10	ENST00000378750.10	NP_004804.2	Q9Y5Y5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX16	ENST00000378750.10 link	c.542-16C>T		intron_variant	Intron 6 of 10	1	NM_004813.4	ENSP00000368024.5		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

GnomAD2 exomes

AF:

0.801

AC:

197084

AN:

246036

AF XY:

0.821

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 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

African (AFR)

AF:

0.574

AC:

19223

AN:

33466

American (AMR)

AF:

0.586

AC:

26185

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.859

AC:

22436

AN:

26124

East Asian (EAS)

AF:

0.381

AC:

15132

AN:

39690

South Asian (SAS)

AF:

0.858

AC:

73969

AN:

86234

European-Finnish (FIN)

AF:

0.937

AC:

44962

AN:

47966

Middle Eastern (MID)

AF:

0.861

AC:

4969

AN:

5768

European-Non Finnish (NFE)

AF:

0.918

AC:

1020905

AN:

1111798

Other (OTH)

AF:

0.855

AC:

51604

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

8457

16914

25372

33829

42286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21296

42592

63888

85184

106480

<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:

0.786

AC:

119539

AN:

152146

Hom.:

49021

Cov.:

AF XY:

0.785

AC XY:

58415

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.588

AC:

24372

AN:

41466

American (AMR)

AF:

0.701

AC:

10724

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.852

AC:

2958

AN:

3470

East Asian (EAS)

AF:

0.434

AC:

2219

AN:

5118

South Asian (SAS)

AF:

0.854

AC:

4119

AN:

4826

European-Finnish (FIN)

AF:

0.945

AC:

10038

AN:

10622

Middle Eastern (MID)

AF:

0.840

AC:

247

AN:

294

European-Non Finnish (NFE)

AF:

0.916

AC:

62328

AN:

68022

Other (OTH)

AF:

0.800

AC:

1689

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1125

2250

3375

4500

5625

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

854

1708

2562

3416

4270

<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:

0.811

Hom.:

12404

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

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

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

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

- -

Aug 07, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

- -

Peroxisome biogenesis disorder 8A (Zellweger)

Benign:1

Sep 05, 2021

Genome-Nilou Lab

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

-0.85

CADD

Benign

0.025

(source)

DANN

Benign

0.53

PhyloP100

-0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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