Variant 4-121801378-G-A 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.-47G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0031 in 1,581,396 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 86 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 76 hom. )

Consequence

EXOSC9
NM_005033.3 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.51

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:

Genome browser will be placed here

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 4-121801378-G-A is Benign according to our data. Variant chr4-121801378-G-A is described in ClinVar as [Benign]. Clinvar id is 1268353.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
EXOSC9	NM_005033.3 linkuse as main transcript	c.-47G>A	5_prime_UTR_variant	1/12	ENST00000243498.10	NP_005024.2	Q06265-1
EXOSC9	NM_001034194.2 linkuse as main transcript	c.-47G>A	5_prime_UTR_variant	1/13		NP_001029366.1	Q06265-2
EXOSC9	XM_011532035.4 linkuse as main transcript	c.-47G>A	5_prime_UTR_variant	1/11		XP_011530337.1	B4DXG8
EXOSC9	XR_007057929.1 linkuse as main transcript	n.56G>A	non_coding_transcript_exon_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOSC9	ENST00000243498 linkuse as main transcript	c.-47G>A		5_prime_UTR_variant	1/12	1	NM_005033.3	ENSP00000243498.5		Q06265-1

Frequencies

GnomAD3 genomes

AF:

0.0160

AC:

2440

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0563

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00451

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00404

AC:

1013

AN:

250988

Hom.:

AF XY:

0.00305

AC XY:

414

AN XY:

135690

show subpopulations

Gnomad AFR exome

AF:

0.0553

Gnomad AMR exome

AF:

0.00258

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.000981

GnomAD4 exome

AF:

0.00172

AC:

2457

AN:

1429078

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

1076

AN XY:

713028

show subpopulations

Gnomad4 AFR exome

AF:

0.0604

Gnomad4 AMR exome

AF:

0.00273

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000164

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000933

Gnomad4 OTH exome

AF:

0.00354

GnomAD4 genome

AF:

0.0161

AC:

2449

AN:

152318

Hom.:

Cov.:

AF XY:

0.0156

AC XY:

1161

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0564

Gnomad4 AMR

AF:

0.00451

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00994

Alfa

AF:

0.00638

Hom.:

Bravo

AF:

0.0179

Asia WGS

AF:

0.00433

AC:

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 21, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.4

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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