6-136822619-A-AACGGCTTCC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000288.4(PEX7):c.-46_-38dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 35)
• Consequence: PEX7 NM_000288.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.83

Genes affected

PEX7 (HGNC:8860): (peroxisomal biogenesis factor 7) This gene encodes the cytosolic receptor for the set of peroxisomal matrix enzymes targeted to the organelle by the peroxisome targeting signal 2 (PTS2). Defects in this gene cause peroxisome biogenesis disorders (PBDs), which are characterized by multiple defects in peroxisome function. There are at least 14 complementation groups for PBDs, with more than one phenotype being observed in cases falling into particular complementation groups. Although the clinical features of PBD patients vary, cells from all PBD patients exhibit a defect in the import of one or more classes of peroxisomal matrix proteins into the organelle. Defects in this gene have been associated with PBD complementation group 11 (PBD-CG11) disorders, rhizomelic chondrodysplasia punctata type 1 (RCDP1), and Refsum disease (RD). [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEX7	NM_000288.4	c.-46_-38dup		5_prime_UTR_variant	1/10	ENST00000318471.5
PEX7	XM_006715502.3	c.-46_-38dup		5_prime_UTR_variant	1/7
PEX7	XM_047418874.1	c.-46_-38dup		5_prime_UTR_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX7	ENST00000318471.5	c.-46_-38dup		5_prime_UTR_variant	1/10	1	NM_000288.4	P1
PEX7	ENST00000367756.8	c.-46_-38dup		5_prime_UTR_variant	1/4	3
PEX7	ENST00000541292.6	c.-46_-38dup		5_prime_UTR_variant, NMD_transcript_variant	1/11	5
PEX7	ENST00000678593.1			upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 35

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Rhizomelic chondrodysplasia punctata type 1 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Counsyl

Apr 30, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1554328233; hg19: chr6-137143757;