dbSNP rs1129333: PEX10:c.*1529T>C (chr1-2404237-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002617.4(PEX10):c.*1529T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 152,190 control chromosomes in the GnomAD database, including 52,526 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 0.82 ( 52519 hom., cov: 32)

Exomes 𝑓: 0.89 ( 7 hom. )

Consequence

PEX10
NM_002617.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0270

Publications

15 publications found

Variant links:

Genes affected

PEX10 (HGNC:8851): (peroxisomal biogenesis factor 10) This gene encodes a protein involved in import of peroxisomal matrix proteins. This protein localizes to the peroxisomal membrane. Mutations in this gene result in phenotypes within the Zellweger spectrum of peroxisomal biogenesis disorders, ranging from neonatal adrenoleukodystrophy to Zellweger syndrome. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

PEX10 links:

RER1 (HGNC:30309): (retention in endoplasmic reticulum sorting receptor 1) The protein encoded by this gene is a multi-pass membrane protein that is localized to the golgi apparatus. It is involved in the retention of endoplasmic reticulum (ER) membrane proteins in the ER and retrieval of ER membrane proteins from the early Golgi compartment to facilitate gamma-secretase complex assembly. [provided by RefSeq, Oct 2009]

RER1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX10	NM_002617.4 link	c.*1529T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000447513.7	NP_002608.1	O60683-1A0A024R068
RER1	NM_007033.5 link	c.*1113A>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000605895.6	NP_008964.3	O15258Q5T094

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX10	ENST00000447513.7 link	c.*1529T>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_002617.4	ENSP00000407922.2		O60683-1
RER1	ENST00000605895.6 link	c.*1113A>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_007033.5	ENSP00000475168.1		O15258

Frequencies

GnomAD3 genomes

AF:

0.823

AC:

125091

AN:

152054

Hom.:

52511

Cov.:

show subpopulations

Gnomad AFR

AF:

0.641

Gnomad AMI

AF:

0.765

Gnomad AMR

AF:

0.828

Gnomad ASJ

AF:

0.916

Gnomad EAS

AF:

0.831

Gnomad SAS

AF:

0.830

Gnomad FIN

AF:

0.928

Gnomad MID

AF:

0.873

Gnomad NFE

AF:

0.910

Gnomad OTH

AF:

0.841

GnomAD4 exome

AF:

0.889

AC:

AN:

Hom.:

Cov.:

AF XY:

0.917

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.750

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.002339), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.350

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

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:

0.822

AC:

125140

AN:

152172

Hom.:

52519

Cov.:

AF XY:

0.823

AC XY:

61249

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.640

AC:

26559

AN:

41468

American (AMR)

AF:

0.828

AC:

12661

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.916

AC:

3182

AN:

3472

East Asian (EAS)

AF:

0.831

AC:

4301

AN:

5176

South Asian (SAS)

AF:

0.829

AC:

3997

AN:

4824

European-Finnish (FIN)

AF:

0.928

AC:

9848

AN:

10612

Middle Eastern (MID)

AF:

0.888

AC:

261

AN:

294

European-Non Finnish (NFE)

AF:

0.910

AC:

61874

AN:

68018

Other (OTH)

AF:

0.835

AC:

1759

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1040

2079

3119

4158

5198

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

882

1764

2646

3528

4410

<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:

0.876

Hom.:

64509

Bravo

AF:

0.806

Asia WGS

AF:

0.785

AC:

2732

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.0

(source)

DANN

Benign

0.40

PhyloP100

0.027

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over