chr11-45910189-A-G
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The ENST00000241041.7(PEX16):c.953-12T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0021 in 1,612,798 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0074 ( 13 hom., cov: 33)
Exomes 𝑓: 0.0016 ( 19 hom. )
Consequence
PEX16
ENST00000241041.7 splice_polypyrimidine_tract, intron
ENST00000241041.7 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.1877
2
Clinical Significance
Conservation
PhyloP100: 1.97
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
?
Variant 11-45910189-A-G is Benign according to our data. Variant chr11-45910189-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 304785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-45910189-A-G is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00739 (1126/152310) while in subpopulation AFR AF= 0.0233 (968/41570). AF 95% confidence interval is 0.0221. There are 13 homozygotes in gnomad4. There are 531 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 13 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PEX16 | NM_004813.4 | c.*65T>C | 3_prime_UTR_variant | 11/11 | ENST00000378750.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX16 | ENST00000378750.10 | c.*65T>C | 3_prime_UTR_variant | 11/11 | 1 | NM_004813.4 | P1 | ||
PEX16 | ENST00000241041.7 | c.953-12T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | |||||
PEX16 | ENST00000523721.2 | n.306T>C | non_coding_transcript_exon_variant | 3/3 | 5 | ||||
PEX16 | ENST00000532681.5 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00737 AC: 1122AN: 152192Hom.: 13 Cov.: 33
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GnomAD3 exomes AF: 0.00278 AC: 697AN: 250450Hom.: 10 AF XY: 0.00205 AC XY: 278AN XY: 135652
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GnomAD4 exome AF: 0.00155 AC: 2266AN: 1460488Hom.: 19 Cov.: 32 AF XY: 0.00146 AC XY: 1060AN XY: 726574
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GnomAD4 genome ? AF: 0.00739 AC: 1126AN: 152310Hom.: 13 Cov.: 33 AF XY: 0.00713 AC XY: 531AN XY: 74486
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Peroxisome biogenesis disorder 8A (Zellweger);C3553960:Peroxisome biogenesis disorder 8B Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 08, 2021 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 01, 2021 | - - |
Peroxisome biogenesis disorder 8A (Zellweger) Benign:1
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at