chr22-18077996-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_001127649.3(PEX26):c.-381C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000314 in 433,566 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00038 ( 1 hom. )

Consequence

PEX26
NM_001127649.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.920

Publications

0 publications found

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]

PEX26 Gene-Disease associations (from GenCC):

peroxisome biogenesis disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
peroxisome biogenesis disorder 7A (Zellweger)
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
peroxisome biogenesis disorder 7B
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics
Zellweger spectrum disorders
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PEX26 links:

ENSG00000288683 (HGNC:):

ENSG00000288683 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00019 (29/152298) while in subpopulation SAS AF = 0.00124 (6/4830). AF 95% confidence interval is 0.000541. There are 0 homozygotes in GnomAd4. There are 13 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127649.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PEX26	NM_001127649.3	MANE Select	c.-381C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_001121121.1	Q7Z412-1
PEX26	NM_001127649.3	MANE Select	c.-381C>T	5_prime_UTR	Exon 1 of 5	NP_001121121.1	Q7Z412-1
PEX26	NM_017929.6		c.-133C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_060399.1	Q7Z412-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PEX26	ENST00000399744.8	TSL:1 MANE Select	c.-381C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000382648.4	Q7Z412-1
PEX26	ENST00000329627.11	TSL:1	c.-133C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000331106.5	Q7Z412-1
PEX26	ENST00000399744.8	TSL:1 MANE Select	c.-381C>T	5_prime_UTR	Exon 1 of 5	ENSP00000382648.4	Q7Z412-1

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.000479

GnomAD4 exome

AF:

0.000380

AC:

107

AN:

281268

Hom.:

Cov.:

AF XY:

0.000481

AC XY:

AN XY:

159960

show subpopulations

African (AFR)

AF:

0.000132

AC:

AN:

7562

American (AMR)

AF:

0.0000491

AC:

AN:

20372

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8634

East Asian (EAS)

AF:

0.00

AC:

AN:

10308

South Asian (SAS)

AF:

0.00106

AC:

AN:

54548

European-Finnish (FIN)

AF:

0.00

AC:

AN:

11460

Middle Eastern (MID)

AF:

0.00

AC:

AN:

984

European-Non Finnish (NFE)

AF:

0.000299

AC:

AN:

154094

Other (OTH)

AF:

0.0000752

AC:

AN:

13306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000190

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.0000962

AC:

AN:

41566

American (AMR)

AF:

0.0000653

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00124

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

68022

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000208

Hom.:

Bravo

AF:

0.000155

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Peroxisome biogenesis disorder 7A (Zellweger) (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

7.2

(source)

DANN

Benign

0.93

PhyloP100

0.92

PromoterAI

-0.056

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over