11-45909951-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.*303C>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 0.628 in 788,526 control chromosomes in the GnomAD database, including 170,113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (26496 hom., cov: 34)
  • Exomes 𝑓: 0.65 (143617 hom.)
• Consequence: PEX16 NM_004813.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.311

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=-0.92).
• BP6: Variant 11-45909951-G-A is Benign according to our data. Variant chr11-45909951-G-A is described in ClinVar as [Benign]. Clinvar id is 304781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEX16	NM_004813.4	c.*303C>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.*303C>T		3_prime_UTR_variant	11/11	1	NM_004813.4	P1
PEX16	ENST00000241041.7	c.*138C>T		3_prime_UTR_variant	11/11	1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81330 AN: 152092 Hom.: 26501 Cov.: 34

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.595

GnomAD4 exome AF: 0.651 AC: 414088 AN: 636316 Hom.: 143617 Cov.: 8 AF XY: 0.653 AC XY: 220714 AN XY: 337832

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.489

Gnomad4 ASJ exome AF: 0.768

Gnomad4 EAS exome AF: 0.155

Gnomad4 SAS exome AF: 0.585

Gnomad4 FIN exome AF: 0.696

Gnomad4 NFE exome AF: 0.731

Gnomad4 OTH exome AF: 0.639

GnomAD4 genome AF: 0.534 AC: 81321 AN: 152210 Hom.: 26496 Cov.: 34 AF XY: 0.532 AC XY: 39610 AN XY: 74406

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.775

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.571

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.730

Gnomad4 OTH AF: 0.598

Alfa AF: 0.697 Hom.: 37162

Bravo AF: 0.507

Asia WGS AF: 0.398 AC: 1390 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

Aug 07, 2018

- -

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	-0.92
Cadd	Benign	0.33
Dann	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10838529; hg19: chr11-45931502; COSMIC: COSV53796581; COSMIC: COSV53796581;