Variant 1-11073948-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000376936.9(EXOSC10):c.2143A>G(p.Thr715Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0033 in 1,612,758 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 3 hom., cov: 30)

Exomes 𝑓: 0.0034 ( 18 hom. )

Consequence

EXOSC10
ENST00000376936.9 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.33

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009223729).

BP6

Variant 1-11073948-T-C is Benign according to our data. Variant chr1-11073948-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2638218.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOSC10	NM_001001998.3 linkuse as main transcript	c.2143A>G	p.Thr715Ala	missense_variant	19/25	ENST00000376936.9	NP_001001998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOSC10	ENST00000376936.9 linkuse as main transcript	c.2143A>G	p.Thr715Ala	missense_variant	19/25	1	NM_001001998.3	ENSP00000366135	P1	Q01780-1
EXOSC10	ENST00000304457.11 linkuse as main transcript	c.2082+283A>G		intron_variant		1		ENSP00000307307		Q01780-2
EXOSC10	ENST00000474216.5 linkuse as main transcript	n.1380A>G		non_coding_transcript_exon_variant	7/13	2

Frequencies

GnomAD3 genomes

AF:

0.00215

AC:

326

AN:

151400

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000657

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00171

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.000192

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00382

Gnomad OTH

AF:

0.00289

GnomAD3 exomes

AF:

0.00179

AC:

451

AN:

251452

Hom.:

AF XY:

0.00189

AC XY:

257

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.000861

Gnomad AMR exome

AF:

0.00188

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00302

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00343

AC:

5005

AN:

1461286

Hom.:

Cov.:

AF XY:

0.00339

AC XY:

2462

AN XY:

726998

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.00206

Gnomad4 ASJ exome

AF:

0.000612

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.00416

Gnomad4 OTH exome

AF:

0.00353

GnomAD4 genome

AF:

0.00215

AC:

325

AN:

151472

Hom.:

Cov.:

AF XY:

0.00184

AC XY:

136

AN XY:

73944

show subpopulations

Gnomad4 AFR

AF:

0.000655

Gnomad4 AMR

AF:

0.00171

Gnomad4 ASJ

AF:

0.000866

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.000192

Gnomad4 NFE

AF:

0.00381

Gnomad4 OTH

AF:

0.00287

Alfa

AF:

0.00232

Hom.:

Bravo

AF:

0.00228

TwinsUK

AF:

0.00836

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00360

AC:

ExAC

AF:

0.00157

AC:

191

EpiCase

AF:

0.00403

EpiControl

AF:

0.00367

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

EXOSC10: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.34

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0041

MetaRNN

Benign

0.0092

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.56

REVEL

Benign

0.052

Sift

Benign

0.091

Sift4G

Benign

0.36

Polyphen

0.0090

Vest4

0.21

MVP

0.53

MPC

0.22

ClinPred

0.0086

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.076

gMVP

0.22

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over