Variant chr1-11073927-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001001998.3(EXOSC10):c.2157+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00513 in 1,429,440 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 2 hom., cov: 30)

Exomes 𝑓: 0.0054 ( 26 hom. )

Consequence

EXOSC10
NM_001001998.3 splice_region, intron

Scores

Splicing: ADA: 0.0001215

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.374

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 (BayesDel_noAF=-0.77).

BP6

Variant 1-11073927-C-T is Benign according to our data. Variant chr1-11073927-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3024718.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOSC10	NM_001001998.3 linkuse as main transcript	c.2157+7G>A		splice_region_variant, intron_variant		ENST00000376936.9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
EXOSC10	ENST00000376936.9 linkuse as main transcript	c.2157+7G>A	splice_region_variant, intron_variant	1	NM_001001998.3	P1	Q01780-1
EXOSC10	ENST00000304457.11 linkuse as main transcript	c.2082+304G>A	intron_variant	1			Q01780-2
EXOSC10	ENST00000474216.5 linkuse as main transcript	n.1394+7G>A	splice_region_variant, intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00289

AC:

430

AN:

148648

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000592

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00189

Gnomad ASJ

AF:

0.00116

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00108

Gnomad FIN

AF:

0.00200

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00513

Gnomad OTH

AF:

0.00196

GnomAD3 exomes

AF:

0.00291

AC:

732

AN:

251286

Hom.:

AF XY:

0.00298

AC XY:

405

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00188

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000948

Gnomad FIN exome

AF:

0.00180

Gnomad NFE exome

AF:

0.00498

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00539

AC:

6902

AN:

1280730

Hom.:

Cov.:

AF XY:

0.00529

AC XY:

3406

AN XY:

644150

show subpopulations

Gnomad4 AFR exome

AF:

0.000443

Gnomad4 AMR exome

AF:

0.00187

Gnomad4 ASJ exome

AF:

0.00112

Gnomad4 EAS exome

AF:

0.0000783

Gnomad4 SAS exome

AF:

0.000918

Gnomad4 FIN exome

AF:

0.00215

Gnomad4 NFE exome

AF:

0.00670

Gnomad4 OTH exome

AF:

0.00441

GnomAD4 genome

AF:

0.00289

AC:

430

AN:

148710

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

197

AN XY:

72204

show subpopulations

Gnomad4 AFR

AF:

0.000591

Gnomad4 AMR

AF:

0.00189

Gnomad4 ASJ

AF:

0.00116

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00108

Gnomad4 FIN

AF:

0.00200

Gnomad4 NFE

AF:

0.00513

Gnomad4 OTH

AF:

0.00194

Alfa

AF:

0.00416

Hom.:

Bravo

AF:

0.00305

EpiCase

AF:

0.00594

EpiControl

AF:

0.00457

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

Feb 01, 2024

EXOSC10: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

4.4

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.10

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