rs797045062

chr11-45910267-TAGA-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1 PM2 PM4_Supporting PP5_Moderate

The NM_004813.4(PEX16):c.995_997del(p.Phe332del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. F332F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PEX16 NM_004813.4 inframe_deletion
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 8.22

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 Likely_pathogenic. Variant got 7 ACMG points.

• PM1: In a region_of_interest Interaction with PEX19 (size 115) in uniprot entity PEX16_HUMAN there are 11 pathogenic changes around while only 0 benign (100%) in NM_004813.4
• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_004813.4. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 11-45910267-TAGA-T is Pathogenic according to our data. Variant chr11-45910267-TAGA-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 209181.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEX16	NM_004813.4	c.995_997del	p.Phe332del	inframe_deletion	11/11	ENST00000378750.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX16	ENST00000378750.10	c.995_997del	p.Phe332del	inframe_deletion	11/11	1	NM_004813.4	P1
PEX16	ENST00000241041.7	c.953-93_953-91del		intron_variant		1
PEX16	ENST00000532681.5	c.710_712del	p.Phe237del	inframe_deletion	11/11	3
PEX16	ENST00000523721.2	n.225_227del		non_coding_transcript_exon_variant	3/3	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: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Peroxisome biogenesis disorder 8B Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Baylor Genetics

Oct 19, 2012

Likely pathogenicity based on finding it once in our laboratory homozygous in a 20-year-old female with intellectual disability, spasticity, ataxia, structural brain abnormalities -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs797045062; hg19: chr11-45931818;