Variant 8-144080595-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_019037.3(EXOSC4):c.732G>A(p.Gly244Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,596,730 control chromosomes in the GnomAD database, including 2 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 0.0010 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 2 hom. )

Consequence

EXOSC4
NM_019037.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.24

Variant links:

Genes affected

EXOSC4 (HGNC:18189): (exosome component 4) Enables mRNA 3'-UTR AU-rich region binding activity. Involved in nucleic acid metabolic process and positive regulation of cell growth. Acts upstream of or within defense response to virus. Located in cytosol; nucleoplasm; and transcriptionally active chromatin. Part of exosome (RNase complex). [provided by Alliance of Genome Resources, Apr 2022]

EXOSC4 links:

ENSG00000290230 (HGNC:):

ENSG00000290230 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP7

Synonymous conserved (PhyloP=1.24 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOSC4	NM_019037.3 linkuse as main transcript	c.732G>A	p.Gly244Gly	synonymous_variant	3/3	ENST00000316052.6	NP_061910.1	Q9NPD3
EXOSC4	XM_011517134.4 linkuse as main transcript	c.438G>A	p.Gly146Gly	synonymous_variant	3/3		XP_011515436.1
LOC124902038	XR_007061141.1 linkuse as main transcript	n.1234C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EXOSC4	ENST00000316052.6 linkuse as main transcript	c.732G>A	p.Gly244Gly	synonymous_variant	3/3	1	NM_019037.3	ENSP00000315476.4	Q9NPD3
ENSG00000290230	ENST00000703646.1 linkuse as main transcript	n.705+27G>A		intron_variant				ENSP00000515414.1	A0A994J4D9
ENSG00000290230	ENST00000703645.1 linkuse as main transcript	n.792+27G>A		intron_variant
EXOSC4	ENST00000527954.1 linkuse as main transcript	c.*16G>A		downstream_gene_variant		2		ENSP00000436539.1	E9PI41

Frequencies

GnomAD3 genomes

AF:

0.00103

AC:

157

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00169

Gnomad OTH

AF:

0.000962

GnomAD3 exomes

AF:

0.00123

AC:

294

AN:

238458

Hom.:

AF XY:

0.00135

AC XY:

175

AN XY:

129992

show subpopulations

Gnomad AFR exome

AF:

0.000127

Gnomad AMR exome

AF:

0.000842

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00131

Gnomad FIN exome

AF:

0.0000851

Gnomad NFE exome

AF:

0.00191

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.00193

AC:

2791

AN:

1444512

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

1373

AN XY:

718656

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000761

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00154

Gnomad4 FIN exome

AF:

0.000103

Gnomad4 NFE exome

AF:

0.00225

Gnomad4 OTH exome

AF:

0.00141

GnomAD4 genome

AF:

0.00104

AC:

158

AN:

152218

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.000458

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00169

Gnomad4 OTH

AF:

0.000951

Alfa

AF:

0.000856

Hom.:

Bravo

AF:

0.000948

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00213

EpiControl

AF:

0.00154

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.1

DANN

Benign

0.76

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