Variant 11-45909816-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.562

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
PEX16	NM_004813.4 linkuse as main transcript	c.*438C>T		3_prime_UTR_variant	11/11	ENST00000378750.10	NP_004804.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX16	ENST00000378750.10 linkuse as main transcript	c.*438C>T		3_prime_UTR_variant	11/11	1	NM_004813.4	ENSP00000368024	P1	Q9Y5Y5-1
PEX16	ENST00000241041.7 linkuse as main transcript	c.*273C>T		3_prime_UTR_variant	11/11	1		ENSP00000241041		Q9Y5Y5-2

Frequencies

GnomAD3 genomes

AF:

0.0218

AC:

3317

AN:

152228

Hom.:

109

Cov.:

show subpopulations

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.:

AF XY:

0.0117

AC XY:

2314

AN XY:

197708

show subpopulations

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.:

AF XY:

0.0220

AC XY:

1640

AN XY:

74498

show subpopulations

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.:

Bravo

AF:

0.0231

Asia WGS

AF:

0.0870

AC:

300

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over