11-45915755-C-T

Position:

chr11-45915755-C-T

Variant summary

Our verdict is Benign. Variant got -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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

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

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:

PEX16 (HGNC:):

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 (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 [Likely_benign]. Clinvar id is 259544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-45915755-C-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
PEX16	NM_004813.4 linkuse as main transcript	c.307G>A	p.Val103Met	missense_variant	4/11	ENST00000378750.10	NP_004804.2	Q9Y5Y5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX16	ENST00000378750.10 linkuse as main transcript	c.307G>A	p.Val103Met	missense_variant	4/11	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

GnomAD3 exomes

AF:

0.0227

AC:

5714

AN:

251380

Hom.:

AF XY:

0.0240

AC XY:

3255

AN XY:

135880

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 SAS exome

AF:

0.0238

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

Gnomad4 AFR exome

AF:

0.00574

Gnomad4 AMR exome

AF:

0.0163

Gnomad4 ASJ exome

AF:

0.0211

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0233

Gnomad4 FIN exome

AF:

0.0256

Gnomad4 NFE exome

AF:

0.0284

Gnomad4 OTH exome

AF:

0.0270

GnomAD4 genome

AF:

0.0199

AC:

3023

AN:

152206

Hom.:

Cov.:

AF XY:

0.0197

AC XY:

1463

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.00486

Gnomad4 AMR

AF:

0.0196

Gnomad4 ASJ

AF:

0.0190

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.0191

Gnomad4 FIN

AF:

0.0276

Gnomad4 NFE

AF:

0.0294

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.0252

Hom.:

103

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

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 31, 2023	See Variant Classification Assertion Criteria. -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Dec 15, 2015	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

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. -

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

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;.;.

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

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