11-45909667-T-C

Variant names:

• chr11-45909667-T-C
• rs72902478
• NM_004813.4:c.*587A>G

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.*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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.124
• Publications: 1 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=-0.91).
• 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
PEX16	NM_004813.4	c.*587A>G		3_prime_UTR_variant	Exon 11 of 11	ENST00000378750.10	NP_004804.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX16	ENST00000378750.10	c.*587A>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_004813.4	ENSP00000368024.5
PEX16	ENST00000241041.7	c.*422A>G		downstream_gene_variant		1		ENSP00000241041.3

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

African (AFR) AF: 0.0148 AC: 44 AN: 2972

American (AMR) AF: 0.0464 AC: 207 AN: 4458

Ashkenazi Jewish (ASJ) AF: 0.0315 AC: 57 AN: 1812

East Asian (EAS) AF: 0.00 AC: 0 AN: 4258

South Asian (SAS) AF: 0.0147 AC: 151 AN: 10270

European-Finnish (FIN) AF: 0.129 AC: 396 AN: 3064

Middle Eastern (MID) AF: 0.0318 AC: 10 AN: 314

European-Non Finnish (NFE) AF: 0.0974 AC: 4348 AN: 44624

Other (OTH) AF: 0.0798 AC: 314 AN: 3936

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

African (AFR) AF: 0.0163 AC: 678 AN: 41582

American (AMR) AF: 0.0541 AC: 827 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0291 AC: 101 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.0157 AC: 76 AN: 4826

European-Finnish (FIN) AF: 0.144 AC: 1527 AN: 10610

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0967 AC: 6576 AN: 68008

Other (OTH) AF: 0.0497 AC: 105 AN: 2114

Alfa AF: 0.0645 Hom.: 152

Bravo AF: 0.0559

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Peroxisome biogenesis disorder 1A (Zellweger) Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.4
DANN	Benign	0.39
PhyloP100		0.12

Splicing

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

Other links and lift over

dbSNP: rs72902478; hg19: chr11-45931218;