NM_004813.4:c.952+118_*82del

Variant names:

• chr11-45910171-TGGGACGCTGCCGGAGTCAGTTTTATTAGGGAAGAGGGGCTCCCTGCCCCACCCCTCCCCACACCCTCCTTCCGGGAGGTCTGTCAGCCCCAACTGTAGAAGTAGATTTTCTGCCAGGTGGGCAAGTAATCCATGAGCGGCCCTGCAGTGGGAGAGGGACACATCAGGGCAGGCCAGACCCCAATCTGCACTGTGGCGCCACATACAGCACCTCACCCCTGCGGCCCAGGAGCCAGCCCAGCTGGCTGTCTTGCCCTGCCCCCAGGAGGCAGCACTGCAGGGGACTCTGGCACCATTTACAAAGACCCTCAGGCCCAGAGAAGCTCAGCCAGGGTAGACACTGAGGGGCCTGAGTCAGGTCCAGTCACCCAACCCAAGCCCAGTGGGCCTCTGCTGAGGGAGGATCTCAGCAGCCCGGTGGACCCCTTCTCTGCCATTGAATCCCCCCAAGATGAGATGGTCCCGTATCGCTCCAGGATACTGTGACCAGAAAAAAGCTGGCAGCTGATGTGGTCCCCCCACCAGTGGACACCCTCCTTCCAGCCATCCCTGGCTCCTCAGGCCACCCTGGCCTATGCCCAGGGGCAGTCCCACCCAATCCTGACTTCCC-T
• NM_004813.4:c.952+118_*82del

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM1 PM4 PP5

The NM_004813.4(PEX16):​c.952+118_*82del​(p.Arg318_Ter337delins???) variant causes a stop lost, conservative inframe deletion, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PEX16 NM_004813.4 stop_lost, conservative_inframe_deletion, splice_region
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.64
• Publications: 0 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: Uncertain_significance. The variant received 5 ACMG points.

• PM1: In a region_of_interest Interaction with PEX19 (size 115) in uniprot entity PEX16_HUMAN there are 7 pathogenic changes around while only 1 benign (88%) in NM_004813.4
• PM4: Stoplost variant in NM_004813.4
• PP5: Variant 11-45910171-TGGGACGCTGCCGGAGTCAGTTTTATTAGGGAAGAGGGGCTCCCTGCCCCACCCCTCCCCACACCCTCCTTCCGGGAGGTCTGTCAGCCCCAACTGTAGAAGTAGATTTTCTGCCAGGTGGGCAAGTAATCCATGAGCGGCCCTGCAGTGGGAGAGGGACACATCAGGGCAGGCCAGACCCCAATCTGCACTGTGGCGCCACATACAGCACCTCACCCCTGCGGCCCAGGAGCCAGCCCAGCTGGCTGTCTTGCCCTGCCCCCAGGAGGCAGCACTGCAGGGGACTCTGGCACCATTTACAAAGACCCTCAGGCCCAGAGAAGCTCAGCCAGGGTAGACACTGAGGGGCCTGAGTCAGGTCCAGTCACCCAACCCAAGCCCAGTGGGCCTCTGCTGAGGGAGGATCTCAGCAGCCCGGTGGACCCCTTCTCTGCCATTGAATCCCCCCAAGATGAGATGGTCCCGTATCGCTCCAGGATACTGTGACCAGAAAAAAGCTGGCAGCTGATGTGGTCCCCCCACCAGTGGACACCCTCCTTCCAGCCATCCCTGGCTCCTCAGGCCACCCTGGCCTATGCCCAGGGGCAGTCCCACCCAATCCTGACTTCCC-T is Pathogenic according to our data. Variant chr11-45910171-TGGGACGCTGCCGGAGTCAGTTTTATTAGGGAAGAGGGGCTCCCTGCCCCACCCCTCCCCACACCCTCCTTCCGGGAGGTCTGTCAGCCCCAACTGTAGAAGTAGATTTTCTGCCAGGTGGGCAAGTAATCCATGAGCGGCCCTGCAGTGGGAGAGGGACACATCAGGGCAGGCCAGACCCCAATCTGCACTGTGGCGCCACATACAGCACCTCACCCCTGCGGCCCAGGAGCCAGCCCAGCTGGCTGTCTTGCCCTGCCCCCAGGAGGCAGCACTGCAGGGGACTCTGGCACCATTTACAAAGACCCTCAGGCCCAGAGAAGCTCAGCCAGGGTAGACACTGAGGGGCCTGAGTCAGGTCCAGTCACCCAACCCAAGCCCAGTGGGCCTCTGCTGAGGGAGGATCTCAGCAGCCCGGTGGACCCCTTCTCTGCCATTGAATCCCCCCAAGATGAGATGGTCCCGTATCGCTCCAGGATACTGTGACCAGAAAAAAGCTGGCAGCTGATGTGGTCCCCCCACCAGTGGACACCCTCCTTCCAGCCATCCCTGGCTCCTCAGGCCACCCTGGCCTATGCCCAGGGGCAGTCCCACCCAATCCTGACTTCCC-T is described in ClinVar as [Pathogenic]. Clinvar id is 30353.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX16	NM_004813.4	c.952+118_*82del	p.Arg318_Ter337delins???	stop_lost, conservative_inframe_deletion, splice_region_variant	Exon 11 of 11	ENST00000378750.10	NP_004804.2
PEX16	NM_004813.4	c.952+118_*82del		splice_acceptor_variant, splice_region_variant, 3_prime_UTR_variant, intron_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.952+118_*82del	p.Arg318_Ter337delins???	stop_lost, conservative_inframe_deletion, splice_region_variant	Exon 11 of 11	1	NM_004813.4	ENSP00000368024.5
PEX16	ENST00000378750.10	c.952+118_*82del		splice_acceptor_variant, splice_region_variant, 3_prime_UTR_variant, intron_variant	Exon 11 of 11	1	NM_004813.4	ENSP00000368024.5

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Peroxisome biogenesis disorder 8B Pathogenic:1

Sep 01, 2010

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6

Splicing

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

Other links and lift over

hg19: chr11-45931722;