dbSNP rs144158336: EXOSC8:c.55-10_55-9delAT (chr13-37002475-CAT-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_181503.3(EXOSC8):c.55-10_55-9delAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00302 in 1,519,264 control chromosomes in the GnomAD database, including 106 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 48 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 58 hom. )

Consequence

EXOSC8
NM_181503.3 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.35

Publications

0 publications found

Variant links:

Genes affected

EXOSC8 (HGNC:17035): (exosome component 8) This gene encodes a 3'-5' exoribonuclease that specifically interacts with mRNAs containing AU-rich elements. The encoded protein is part of the exosome complex that is important for the degradation of numerous RNA species. A pseudogene of this gene is found on chromosome 6. [provided by RefSeq, Mar 2009]

EXOSC8 Gene-Disease associations (from GenCC):

pontocerebellar hypoplasia, type 1C
Inheritance: AR, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
pontocerebellar hypoplasia type 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

EXOSC8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 13-37002475-CAT-C is Benign according to our data. Variant chr13-37002475-CAT-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 235309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOSC8	NM_181503.3 link	c.55-10_55-9delAT		intron_variant	Intron 2 of 10	ENST00000389704.4	NP_852480.1	Q96B26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOSC8	ENST00000389704.4 link	c.55-10_55-9delAT		intron_variant	Intron 2 of 10	1	NM_181503.3	ENSP00000374354.3		Q96B26

Frequencies

GnomAD3 genomes

AF:

0.0158

AC:

2404

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0554

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00497

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.00413

AC:

932

AN:

225694

AF XY:

0.00310

show subpopulations

Gnomad AFR exome

AF:

0.0581

Gnomad AMR exome

AF:

0.00181

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000122

Gnomad FIN exome

AF:

0.0000483

Gnomad NFE exome

AF:

0.0000764

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.00160

AC:

2183

AN:

1367112

Hom.:

AF XY:

0.00146

AC XY:

997

AN XY:

681922

show subpopulations

African (AFR)

AF:

0.0605

AC:

1829

AN:

30242

American (AMR)

AF:

0.00215

AC:

AN:

38106

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24246

East Asian (EAS)

AF:

0.0000518

AC:

AN:

38620

South Asian (SAS)

AF:

0.000158

AC:

AN:

76190

European-Finnish (FIN)

AF:

0.0000388

AC:

AN:

51610

Middle Eastern (MID)

AF:

0.000750

AC:

AN:

5336

European-Non Finnish (NFE)

AF:

0.0000765

AC:

AN:

1046214

Other (OTH)

AF:

0.00304

AC:

172

AN:

56548

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

192

289

385

481

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

186

248

310

<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:

0.0158

AC:

2409

AN:

152152

Hom.:

Cov.:

AF XY:

0.0156

AC XY:

1161

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0554

AC:

2299

AN:

41494

American (AMR)

AF:

0.00497

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68002

Other (OTH)

AF:

0.0104

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

125

251

376

502

627

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.00771

Hom.:

Bravo

AF:

0.0178

Asia WGS

AF:

0.00260

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 11, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pontocerebellar hypoplasia, type 1C

Benign:1

Jan 13, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.3

Mutation Taster

=100/0

polymorphism

(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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over