rs797045062

Variant names:

• chr11-45910267-TAGA-T
• rs797045062
• NM_004813.4:c.995_997delTCT

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PM4_Supporting PP5_Moderate

The NM_004813.4(PEX16):​c.995_997delTCT​(p.Phe332del) variant causes a disruptive 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 disruptive_inframe_deletion
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 8.22
• Publications: 3 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.

• 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 VariationId is 209181.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004813.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX16	NM_004813.4	MANE Select	c.995_997delTCT	p.Phe332del	disruptive_inframe_deletion	Exon 11 of 11	NP_004804.2	Q9Y5Y5-1
	PEX16	NM_057174.3		c.953-93_953-91delTCT		intron	N/A	NP_476515.2	Q9Y5Y5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX16	ENST00000378750.10	TSL:1 MANE Select	c.995_997delTCT	p.Phe332del	disruptive_inframe_deletion	Exon 11 of 11	ENSP00000368024.5	Q9Y5Y5-1
	PEX16	ENST00000241041.7	TSL:1	c.953-93_953-91delTCT		intron	N/A	ENSP00000241041.3	Q9Y5Y5-2
	PEX16	ENST00000905948.1		c.1046_1048delTCT	p.Phe349del	disruptive_inframe_deletion	Exon 11 of 11	ENSP00000576007.1

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

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Peroxisome biogenesis disorder 8B (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.2
Mutation Taster		=9/91	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs797045062; hg19: chr11-45931818;