22-18078014-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_StrongBS1

The NM_001127649.3(PEX26):​c.-363G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 465,028 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

PEX26
NM_001127649.3 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0610
Variant links:
Genes affected
PEX26 (HGNC:22965): (peroxisomal biogenesis factor 26) This gene belongs to the peroxin-26 gene family. It is probably required for protein import into peroxisomes. It anchors PEX1 and PEX6 to peroxisome membranes, possibly to form heteromeric AAA ATPase complexes required for the import of proteins into peroxisomes. Defects in this gene are the cause of peroxisome biogenesis disorder complementation group 8 (PBD-CG8). PBD refers to a group of peroxisomal disorders arising from a failure of protein import into the peroxisomal membrane or matrix. The PBD group is comprised of four disorders: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Dec 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000328 (5/152288) while in subpopulation SAS AF= 0.00103 (5/4832). AF 95% confidence interval is 0.000408. There are 0 homozygotes in gnomad4. There are 4 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PEX26NM_001127649.3 linkc.-363G>T 5_prime_UTR_variant Exon 1 of 5 ENST00000399744.8 NP_001121121.1 Q7Z412-1A0A024R100
PEX26NM_017929.6 linkc.-115G>T 5_prime_UTR_variant Exon 1 of 6 NP_060399.1 Q7Z412-1A0A024R100
PEX26NM_001199319.2 linkc.-115G>T 5_prime_UTR_variant Exon 1 of 5 NP_001186248.1 Q7Z412-2Q7Z2D7A0A0S2Z5M7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PEX26ENST00000399744 linkc.-363G>T 5_prime_UTR_variant Exon 1 of 5 1 NM_001127649.3 ENSP00000382648.4 Q7Z412-1
ENSG00000288683ENST00000474897.6 linkn.-115G>T non_coding_transcript_exon_variant Exon 1 of 9 5 ENSP00000434235.2 E9PRC5
ENSG00000288683ENST00000474897.6 linkn.-115G>T 5_prime_UTR_variant Exon 1 of 9 5 ENSP00000434235.2 E9PRC5

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152172
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00103
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.000224
AC:
70
AN:
312740
Hom.:
1
Cov.:
0
AF XY:
0.000350
AC XY:
62
AN XY:
177014
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:
0.00118
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000667
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152288
Hom.:
0
Cov.:
32
AF XY:
0.0000537
AC XY:
4
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00103
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.76
DANN
Benign
0.80
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: rs138787474; hg19: chr22-18560780; API