6-136822796-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2

The NM_000288.4(PEX7):​c.130+1G>T variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000861 in 1,162,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 8.6e-7 ( 0 hom. )

Consequence

PEX7
NM_000288.4 splice_donor, intron

Scores

5
1
1
Splicing: ADA: 1.000
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.75
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.20987654 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PEX7NM_000288.4 linkc.130+1G>T splice_donor_variant, intron_variant Intron 1 of 9 ENST00000318471.5 NP_000279.1 O00628-1Q6FGN1
PEX7XM_006715502.3 linkc.130+1G>T splice_donor_variant, intron_variant Intron 1 of 6 XP_006715565.1
PEX7XM_047418874.1 linkc.130+1G>T splice_donor_variant, intron_variant Intron 1 of 5 XP_047274830.1
PEX7NM_001410945.1 linkc.-568G>T upstream_gene_variant NP_001397874.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PEX7ENST00000318471.5 linkc.130+1G>T splice_donor_variant, intron_variant Intron 1 of 9 1 NM_000288.4 ENSP00000315680.3 O00628-1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
8.61e-7
AC:
1
AN:
1162078
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
561660
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000103
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.32
CADD
Pathogenic
34
DANN
Uncertain
0.99
Eigen
Pathogenic
1.2
Eigen_PC
Pathogenic
1.0
FATHMM_MKL
Pathogenic
0.97
D
GERP RS
5.3

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.92
SpliceAI score (max)
0.99
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.99
Position offset: -1

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.

Other links and lift over

dbSNP: rs267608253; hg19: chr6-137143934; API