chr6-136822674-GGTGTGCGGT-AGTAGCGGG

Position:

• chr6-136822674-GGTGTGCGGT-AGTAGCGGG

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_000288.4(PEX7):​c.9_18delGGTGTGCGGTinsAGTAGCGGG​(p.Cys5fs) variant causes a frameshift, missense 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 Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: PEX7 NM_000288.4 frameshift, missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 1.99

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 Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 39 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 6-136822674-GGTGTGCGGT-AGTAGCGGG is Pathogenic according to our data. Variant chr6-136822674-GGTGTGCGGT-AGTAGCGGG is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3593202.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX7	NM_000288.4	c.9_18delGGTGTGCGGTinsAGTAGCGGG	p.Cys5fs	frameshift_variant, missense_variant	1/10	ENST00000318471.5	NP_000279.1
PEX7	XM_006715502.3	c.9_18delGGTGTGCGGTinsAGTAGCGGG	p.Cys5fs	frameshift_variant, missense_variant	1/7		XP_006715565.1
PEX7	XM_047418874.1	c.9_18delGGTGTGCGGTinsAGTAGCGGG	p.Cys5fs	frameshift_variant, missense_variant	1/6		XP_047274830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX7	ENST00000318471.5	c.9_18delGGTGTGCGGTinsAGTAGCGGG	p.Cys5fs	frameshift_variant, missense_variant	1/10	1	NM_000288.4	ENSP00000315680.3
PEX7	ENST00000367756.8	c.9_18delGGTGTGCGGTinsAGTAGCGGG	p.Cys5fs	frameshift_variant, missense_variant	1/4	3		ENSP00000356730.4
PEX7	ENST00000541292.6	n.9_18delGGTGTGCGGTinsAGTAGCGGG		non_coding_transcript_exon_variant	1/11	5		ENSP00000441004.1
PEX7	ENST00000678593.1	n.9_18delGGTGTGCGGTinsAGTAGCGGG		non_coding_transcript_exon_variant	1/8			ENSP00000503841.1

Frequencies

GnomAD3 genomes Cov.: 34

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

GnomAD4 genome Cov.: 34

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Rhizomelic chondrodysplasia punctata type 1;C2749346:Peroxisome biogenesis disorder 9B Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jun 06, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-137143812;