Variant 6-42978266-TACCTGAATTCTGAGCTCTCCCATTTCCAGGGGGTCACAGCCAAGATTAAAAGCCAAAGTGGCAGGGACAAGCGCCAGTCCGTCAGCGAGGGGCTCTCCCAGCGGTCCAGAGCCGGGTCCCAGTCTATCAGAGAGGTCCCAGCGAGGTTCTAGGACCTGCACCCTAGCCAAGTGCGGCTGTGAAGTGTTCGATGACTCTCTGGCCTGGGCCACCCACACCCATTCGCCCTGGAAGAGGCCAAGGCCACGGAGACAGCTCCGGCTC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_000287.4(PEX6):c.621_882+2del(p.Ser208fs) variant causes a frameshift, splice donor, splice region, intron change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 31)

Consequence

PEX6
NM_000287.4 frameshift, splice_donor, splice_region, intron

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.55

Variant links:

Genes affected

PEX6 (HGNC:8859): (peroxisomal biogenesis factor 6) This gene encodes a member of the AAA (ATPases associated with diverse cellular activities) family of ATPases. This member is a predominantly cytoplasmic protein, which plays a direct role in peroxisomal protein import and is required for PTS1 (peroxisomal targeting signal 1, a C-terminal tripeptide of the sequence ser-lys-leu) receptor activity. Mutations in this gene cause peroxisome biogenesis disorders of complementation group 4 and complementation group 6. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

PEX6 links:

PEX6 (HGNC:):

PEX6 links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 6-42978266-TACCTGAATTCTGAGCTCTCCCATTTCCAGGGGGTCACAGCCAAGATTAAAAGCCAAAGTGGCAGGGACAAGCGCCAGTCCGTCAGCGAGGGGCTCTCCCAGCGGTCCAGAGCCGGGTCCCAGTCTATCAGAGAGGTCCCAGCGAGGTTCTAGGACCTGCACCCTAGCCAAGTGCGGCTGTGAAGTGTTCGATGACTCTCTGGCCTGGGCCACCCACACCCATTCGCCCTGGAAGAGGCCAAGGCCACGGAGACAGCTCCGGCTC-T is Pathogenic according to our data. Variant chr6-42978266-TACCTGAATTCTGAGCTCTCCCATTTCCAGGGGGTCACAGCCAAGATTAAAAGCCAAAGTGGCAGGGACAAGCGCCAGTCCGTCAGCGAGGGGCTCTCCCAGCGGTCCAGAGCCGGGTCCCAGTCTATCAGAGAGGTCCCAGCGAGGTTCTAGGACCTGCACCCTAGCCAAGTGCGGCTGTGAAGTGTTCGATGACTCTCTGGCCTGGGCCACCCACACCCATTCGCCCTGGAAGAGGCCAAGGCCACGGAGACAGCTCCGGCTC-T is described in ClinVar as [Pathogenic]. Clinvar id is 8125.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX6	NM_000287.4 linkuse as main transcript	c.621_882+2del	p.Ser208fs	frameshift_variant, splice_donor_variant, splice_region_variant, intron_variant	1/17	ENST00000304611.13	NP_000278.3	Q13608-1A0A024RD09

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX6	ENST00000304611.13 linkuse as main transcript	c.621_882+2del	p.Ser208fs	frameshift_variant, splice_donor_variant, splice_region_variant, intron_variant	1/17	1	NM_000287.4	ENSP00000303511.8		Q13608-1
PEX6	ENST00000244546.4 linkuse as main transcript	c.621_882+2del	p.Ser208fs	frameshift_variant, splice_donor_variant, splice_region_variant, intron_variant	1/15	1		ENSP00000244546.4		Q13608-2

Frequencies

GnomAD3 genomes

Cov.:

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

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Peroxisome biogenesis disorder 4B

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 01, 2001

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.