Variant chr4-121801538-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005033.3(EXOSC9):c.66+48C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 1,581,306 control chromosomes in the GnomAD database, including 117,646 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8721 hom., cov: 33)

Exomes 𝑓: 0.39 ( 108925 hom. )

Consequence

EXOSC9
NM_005033.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.169

Variant links:

Genes affected

EXOSC9 (HGNC:9137): (exosome component 9) This gene encodes a component of the human exosome, a exoribonuclease complex which processes and degrades RNA in the nucleus and cytoplasm. This component may play a role in mRNA degradation and the polymyositis/scleroderma autoantigen complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

EXOSC9 links:

EXOSC9 (HGNC:):

EXOSC9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 4-121801538-C-G is Benign according to our data. Variant chr4-121801538-C-G is described in ClinVar as [Benign]. Clinvar id is 1231118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
EXOSC9	NM_005033.3 linkuse as main transcript	c.66+48C>G	intron_variant	ENST00000243498.10	NP_005024.2	Q06265-1
EXOSC9	NM_001034194.2 linkuse as main transcript	c.66+48C>G	intron_variant		NP_001029366.1	Q06265-2
EXOSC9	XM_011532035.4 linkuse as main transcript	c.66+48C>G	intron_variant		XP_011530337.1	B4DXG8
EXOSC9	XR_007057929.1 linkuse as main transcript	n.168+48C>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOSC9	ENST00000243498.10 linkuse as main transcript	c.66+48C>G		intron_variant		1	NM_005033.3	ENSP00000243498.5		Q06265-1

Frequencies

GnomAD3 genomes

AF:

0.318

AC:

48337

AN:

152086

Hom.:

8712

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.370

Gnomad AMR

AF:

0.412

Gnomad ASJ

AF:

0.362

Gnomad EAS

AF:

0.441

Gnomad SAS

AF:

0.339

Gnomad FIN

AF:

0.404

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.378

Gnomad OTH

AF:

0.319

GnomAD3 exomes

AF:

0.378

AC:

94418

AN:

249526

Hom.:

18794

AF XY:

0.376

AC XY:

50700

AN XY:

135020

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.514

Gnomad ASJ exome

AF:

0.357

Gnomad EAS exome

AF:

0.418

Gnomad SAS exome

AF:

0.321

Gnomad FIN exome

AF:

0.409

Gnomad NFE exome

AF:

0.377

Gnomad OTH exome

AF:

0.392

GnomAD4 exome

AF:

0.386

AC:

551900

AN:

1429104

Hom.:

108925

Cov.:

AF XY:

0.383

AC XY:

273048

AN XY:

712848

show subpopulations

Gnomad4 AFR exome

AF:

0.130

Gnomad4 AMR exome

AF:

0.499

Gnomad4 ASJ exome

AF:

0.350

Gnomad4 EAS exome

AF:

0.491

Gnomad4 SAS exome

AF:

0.327

Gnomad4 FIN exome

AF:

0.421

Gnomad4 NFE exome

AF:

0.390

Gnomad4 OTH exome

AF:

0.374

GnomAD4 genome

AF:

0.318

AC:

48360

AN:

152202

Hom.:

8721

Cov.:

AF XY:

0.322

AC XY:

23928

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.138

Gnomad4 AMR

AF:

0.413

Gnomad4 ASJ

AF:

0.362

Gnomad4 EAS

AF:

0.440

Gnomad4 SAS

AF:

0.340

Gnomad4 FIN

AF:

0.404

Gnomad4 NFE

AF:

0.378

Gnomad4 OTH

AF:

0.320

Alfa

AF:

0.342

Hom.:

1709

Bravo

AF:

0.310

Asia WGS

AF:

0.368

AC:

1282

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

4.4

DANN

Benign

0.74

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