11-45909816-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004813.4(PEX16):c.*438C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 530,004 control chromosomes in the GnomAD database, including 214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (109 hom., cov: 34)
  • Exomes 𝑓: 0.010 (105 hom.)
• Consequence: PEX16 NM_004813.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.562

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-45909816-G-A is Benign according to our data. Variant chr11-45909816-G-A is described in ClinVar as [Benign]. Clinvar id is 304775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEX16	NM_004813.4	c.*438C>T		3_prime_UTR_variant	11/11	ENST00000378750.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX16	ENST00000378750.10	c.*438C>T		3_prime_UTR_variant	11/11	1	NM_004813.4	P1
PEX16	ENST00000241041.7	c.*273C>T		3_prime_UTR_variant	11/11	1

Frequencies

GnomAD3 genomes AF: 0.0218 AC: 3317 AN: 152228 Hom.: 109 Cov.: 34

Gnomad AFR AF: 0.0638

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00818

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.0321

Gnomad SAS AF: 0.0505

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.0196

GnomAD4 exome AF: 0.0104 AC: 3936 AN: 377658 Hom.: 105 Cov.: 0 AF XY: 0.0117 AC XY: 2314 AN XY: 197708

Gnomad4 AFR exome AF: 0.0674

Gnomad4 AMR exome AF: 0.00436

Gnomad4 ASJ exome AF: 0.00229

Gnomad4 EAS exome AF: 0.0314

Gnomad4 SAS exome AF: 0.0425

Gnomad4 FIN exome AF: 0.00345

Gnomad4 NFE exome AF: 0.000724

Gnomad4 OTH exome AF: 0.0113

GnomAD4 genome AF: 0.0218 AC: 3314 AN: 152346 Hom.: 109 Cov.: 34 AF XY: 0.0220 AC XY: 1640 AN XY: 74498

Gnomad4 AFR AF: 0.0636

Gnomad4 AMR AF: 0.00817

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.0318

Gnomad4 SAS AF: 0.0503

Gnomad4 FIN AF: 0.00273

Gnomad4 NFE AF: 0.000720

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0119 Hom.: 11

Bravo AF: 0.0231

Asia WGS AF: 0.0870 AC: 300 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 20, 2019

- -

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
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.81
Dann	Benign	0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2280328; hg19: chr11-45931367;