Genetic Variant EXOSC10:c.2158-410C>A (chr1-11072581-G-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_001001998.3(EXOSC10):c.2158-410C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 172,080 control chromosomes in the GnomAD database, including 36,046 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 0.60 ( 31107 hom., cov: 33)

Exomes 𝑓: 0.69 ( 4939 hom. )

Consequence

EXOSC10
NM_001001998.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.83

Publications

5 publications found

Variant links:

Genes affected

EXOSC10 (HGNC:9138): (exosome component 10) Enables 3'-5'-exoribonuclease activity. Involved in several processes, including RNA catabolic process; maturation of 5.8S rRNA; and negative regulation of telomere maintenance via telomerase. Located in cytosol; nuclear lumen; and transcriptionally active chromatin. Part of nuclear exosome (RNase complex). [provided by Alliance of Genome Resources, Apr 2022]

EXOSC10 links:

EXOSC10-AS1 (HGNC:40456): (EXOSC10 antisense RNA 1)

EXOSC10-AS1 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001998.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOSC10	NM_001001998.3	MANE Select	c.2158-410C>A		intron	N/A	NP_001001998.1	Q01780-1
	EXOSC10	NM_002685.4		c.2083-410C>A		intron	N/A	NP_002676.1	Q01780-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EXOSC10	ENST00000376936.9	TSL:1 MANE Select	c.2158-410C>A	intron	N/A	ENSP00000366135.4	Q01780-1
EXOSC10	ENST00000304457.11	TSL:1	c.2083-410C>A	intron	N/A	ENSP00000307307.7	Q01780-2
EXOSC10	ENST00000921096.1		c.2203-410C>A	intron	N/A	ENSP00000591155.1

Frequencies

GnomAD3 genomes

AF:

0.604

AC:

91871

AN:

152022

Hom.:

31093

Cov.:

show subpopulations

Gnomad AFR

AF:

0.267

Gnomad AMI

AF:

0.783

Gnomad AMR

AF:

0.732

Gnomad ASJ

AF:

0.593

Gnomad EAS

AF:

0.785

Gnomad SAS

AF:

0.715

Gnomad FIN

AF:

0.718

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.738

Gnomad OTH

AF:

0.636

GnomAD4 exome

AF:

0.694

AC:

13833

AN:

19940

Hom.:

4939

Cov.:

AF XY:

0.691

AC XY:

7402

AN XY:

10712

show subpopulations

African (AFR)

AF:

0.187

AC:

AN:

422

American (AMR)

AF:

0.735

AC:

1751

AN:

2382

Ashkenazi Jewish (ASJ)

AF:

0.523

AC:

246

AN:

470

East Asian (EAS)

AF:

0.711

AC:

577

AN:

812

South Asian (SAS)

AF:

0.694

AC:

1830

AN:

2638

European-Finnish (FIN)

AF:

0.639

AC:

363

AN:

568

Middle Eastern (MID)

AF:

0.630

AC:

AN:

European-Non Finnish (NFE)

AF:

0.716

AC:

8338

AN:

11642

Other (OTH)

AF:

0.646

AC:

620

AN:

960

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

186

373

559

746

932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

220

330

440

550

<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:

0.604

AC:

91906

AN:

152140

Hom.:

31107

Cov.:

AF XY:

0.608

AC XY:

45226

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.267

AC:

11078

AN:

41492

American (AMR)

AF:

0.732

AC:

11193

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.593

AC:

2057

AN:

3468

East Asian (EAS)

AF:

0.786

AC:

4071

AN:

5182

South Asian (SAS)

AF:

0.716

AC:

3453

AN:

4822

European-Finnish (FIN)

AF:

0.718

AC:

7580

AN:

10562

Middle Eastern (MID)

AF:

0.707

AC:

208

AN:

294

European-Non Finnish (NFE)

AF:

0.738

AC:

50203

AN:

68002

Other (OTH)

AF:

0.638

AC:

1349

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1556

3112

4669

6225

7781

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

746

1492

2238

2984

3730

<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:

0.647

Hom.:

9590

Bravo

AF:

0.591

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.12

(source)

DANN

Benign

0.48

PhyloP100

-1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over