11-45915755-C-T

Variant names:

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.307G>A(p.Val103Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0257 in 1,613,992 control chromosomes in the GnomAD database, including 634 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V103L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.020 ( 47 hom., cov: 31)

Exomes 𝑓: 0.026 ( 587 hom. )

Consequence

PEX16
NM_004813.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.03

Publications

14 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 (MetaRNN=0.010723561).

BP6

Variant 11-45915755-C-T is Benign according to our data. Variant chr11-45915755-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 259544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX16	NM_004813.4 link	c.307G>A	p.Val103Met	missense_variant	Exon 4 of 11	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.307G>A	p.Val103Met	missense_variant	Exon 4 of 11	1	NM_004813.4	ENSP00000368024.5		Q9Y5Y5-1

Frequencies

GnomAD3 genomes

AF:

0.0199

AC:

3024

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00488

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0196

Gnomad ASJ

AF:

0.0190

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.0189

Gnomad FIN

AF:

0.0276

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0294

Gnomad OTH

AF:

0.0235

GnomAD2 exomes

AF:

0.0227

AC:

5714

AN:

251380

AF XY:

0.0240

show subpopulations

Gnomad AFR exome

AF:

0.00406

Gnomad AMR exome

AF:

0.0156

Gnomad ASJ exome

AF:

0.0220

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0267

Gnomad NFE exome

AF:

0.0297

Gnomad OTH exome

AF:

0.0329

GnomAD4 exome

AF:

0.0263

AC:

38434

AN:

1461786

Hom.:

587

Cov.:

AF XY:

0.0265

AC XY:

19299

AN XY:

727200

show subpopulations

African (AFR)

AF:

0.00574

AC:

192

AN:

33478

American (AMR)

AF:

0.0163

AC:

730

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0211

AC:

551

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0233

AC:

2011

AN:

86256

European-Finnish (FIN)

AF:

0.0256

AC:

1367

AN:

53400

Middle Eastern (MID)

AF:

0.0593

AC:

342

AN:

5768

European-Non Finnish (NFE)

AF:

0.0284

AC:

31608

AN:

1111928

Other (OTH)

AF:

0.0270

AC:

1631

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

2045

4091

6136

8182

10227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1176

2352

3528

4704

5880

<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:

0.0199

AC:

3023

AN:

152206

Hom.:

Cov.:

AF XY:

0.0197

AC XY:

1463

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.00486

AC:

202

AN:

41546

American (AMR)

AF:

0.0196

AC:

299

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0190

AC:

AN:

3472

East Asian (EAS)

AF:

0.000195

AC:

AN:

5140

South Asian (SAS)

AF:

0.0191

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0276

AC:

293

AN:

10610

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0294

AC:

2001

AN:

68018

Other (OTH)

AF:

0.0232

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

143

286

428

571

714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0253

Hom.:

217

Bravo

AF:

0.0190

TwinsUK

AF:

0.0229

AC:

ALSPAC

AF:

0.0285

AC:

110

ESP6500AA

AF:

0.00567

AC:

ESP6500EA

AF:

0.0270

AC:

232

ExAC

AF:

0.0234

AC:

2837

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.0328

EpiControl

AF:

0.0299

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 15, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 31, 2023

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.051

.;T;.;T

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.92

D;D;D;D

MetaRNN

Benign

0.011

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L;.;.

PhyloP100

2.0

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.83

N;N;N;N

REVEL

Benign

0.058

Sift

Benign

0.041

D;T;D;T

Sift4G

Benign

0.086

T;T;T;.

Polyphen

0.71

P;P;.;.

Vest4

0.17

MPC

0.47

ClinPred

0.012

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.25

Mutation Taster

=87/13

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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