11-45909667-T-C

Position:

• chr11-45909667-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004813.4(PEX16):​c.*587A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0678 in 227,992 control chromosomes in the GnomAD database, including 766 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.065 (467 hom., cov: 34)
  • Exomes 𝑓: 0.073 (299 hom.)
• Consequence: PEX16 NM_004813.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.124

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-45909667-T-C is Benign according to our data. Variant chr11-45909667-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 368962.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEX16	NM_004813.4	c.*587A>G		3_prime_UTR_variant	11/11	ENST00000378750.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX16	ENST00000378750.10	c.*587A>G		3_prime_UTR_variant	11/11	1	NM_004813.4	P1
PEX16	ENST00000241041.7			downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.0653 AC: 9933 AN: 152166 Hom.: 467 Cov.: 34

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0541

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0967

Gnomad OTH AF: 0.0502

GnomAD4 exome AF: 0.0730 AC: 5527 AN: 75708 Hom.: 299 Cov.: 0 AF XY: 0.0673 AC XY: 2690 AN XY: 39960

Gnomad4 AFR exome AF: 0.0148

Gnomad4 AMR exome AF: 0.0464

Gnomad4 ASJ exome AF: 0.0315

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0147

Gnomad4 FIN exome AF: 0.129

Gnomad4 NFE exome AF: 0.0974

Gnomad4 OTH exome AF: 0.0798

GnomAD4 genome AF: 0.0652 AC: 9930 AN: 152284 Hom.: 467 Cov.: 34 AF XY: 0.0656 AC XY: 4885 AN XY: 74456

Gnomad4 AFR AF: 0.0163

Gnomad4 AMR AF: 0.0541

Gnomad4 ASJ AF: 0.0291

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0157

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.0967

Gnomad4 OTH AF: 0.0497

Alfa AF: 0.0838 Hom.: 146

Bravo AF: 0.0559

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Peroxisome biogenesis disorder 1A (Zellweger) Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.4
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs72902478; hg19: chr11-45931218;