chr11-45914484-G-A

Variant names:

• chr11-45914484-G-A
• rs3802758
• NM_004813.4:c.542-16C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.834
• Publications: 23 publications found

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004813.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX16	NM_004813.4	MANE Select	c.542-16C>T		intron	N/A	NP_004804.2
	PEX16	NM_057174.3		c.542-16C>T		intron	N/A	NP_476515.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX16	ENST00000378750.10	TSL:1 MANE Select	c.542-16C>T		intron	N/A	ENSP00000368024.5
	PEX16	ENST00000241041.7	TSL:1	c.542-16C>T		intron	N/A	ENSP00000241041.3
	PEX16	ENST00000532681.5	TSL:3	c.257-16C>T		intron	N/A	ENSP00000434654.1

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119480 AN: 152028 Hom.: 49004 Cov.: 34

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

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.: 58 AF XY: 0.880 AC XY: 637714 AN XY: 724562

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

GnomAD4 genome AF: 0.786 AC: 119539 AN: 152146 Hom.: 49021 Cov.: 34 AF XY: 0.785 AC XY: 58415 AN XY: 74386

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

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

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

Aug 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.025
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)

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

Other links and lift over

dbSNP: rs3802758; hg19: chr11-45936035; COSMIC: COSV53801994; COSMIC: COSV53801994;