Genetic Variant NM_002617.4:c.*995G>A (chr1-2404771-C-T) – 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.*995G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,352 control chromosomes in the GnomAD database, including 5,211 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 0.25 ( 5206 hom., cov: 34)

Exomes 𝑓: 0.28 ( 5 hom. )

Consequence

PEX10
NM_002617.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.43

Publications

16 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:

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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 (EAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX10	NM_002617.4 link	c.*995G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000447513.7	NP_002608.1	O60683-1A0A024R068
RER1	NM_007033.5 link	c.*1647C>T		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.*995G>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_002617.4	ENSP00000407922.2		O60683-1
RER1	ENST00000605895.6 link	c.*1647C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_007033.5	ENSP00000475168.1		O15258

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37433

AN:

152134

Hom.:

5205

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.302

Gnomad AMR

AF:

0.260

Gnomad ASJ

AF:

0.410

Gnomad EAS

AF:

0.391

Gnomad SAS

AF:

0.252

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.255

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.272

GnomAD4 exome

AF:

0.280

AC:

AN:

100

Hom.:

Cov.:

AF XY:

0.241

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.292

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.246

AC:

37437

AN:

152252

Hom.:

5206

Cov.:

AF XY:

0.244

AC XY:

18182

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.119

AC:

4929

AN:

41554

American (AMR)

AF:

0.260

AC:

3985

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.410

AC:

1423

AN:

3470

East Asian (EAS)

AF:

0.391

AC:

2025

AN:

5176

South Asian (SAS)

AF:

0.251

AC:

1214

AN:

4832

European-Finnish (FIN)

AF:

0.246

AC:

2605

AN:

10602

Middle Eastern (MID)

AF:

0.260

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.299

AC:

20331

AN:

67994

Other (OTH)

AF:

0.271

AC:

574

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1486

2972

4459

5945

7431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.294

Hom.:

7865

Bravo

AF:

0.247

Asia WGS

AF:

0.274

AC:

953

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

0.55

(source)

DANN

Benign

0.75

PhyloP100

-1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over