Variant 8-144079996-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_019037.3(EXOSC4):c.225A>G(p.Gln75Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00661 in 1,614,074 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0068 ( 43 hom. )

Consequence

EXOSC4
NM_019037.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.07

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 8-144079996-A-G is Benign according to our data. Variant chr8-144079996-A-G is described in ClinVar as [Benign]. Clinvar id is 774253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.07 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 43 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOSC4	NM_019037.3 linkuse as main transcript	c.225A>G	p.Gln75Gln	synonymous_variant	2/3	ENST00000316052.6	NP_061910.1	Q9NPD3
EXOSC4	XM_011517134.4 linkuse as main transcript	c.-70A>G		5_prime_UTR_variant	2/3		XP_011515436.1
LOC124902038	XR_007061141.1 linkuse as main transcript	n.1833T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOSC4	ENST00000316052.6 linkuse as main transcript	c.225A>G	p.Gln75Gln	synonymous_variant	2/3	1	NM_019037.3	ENSP00000315476.4		Q9NPD3
ENSG00000290230	ENST00000703646.1 linkuse as main transcript	n.225A>G		non_coding_transcript_exon_variant	2/8			ENSP00000515414.1		A0A994J4D9

Frequencies

GnomAD3 genomes

AF:

0.00450

AC:

685

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.00456

Gnomad FIN

AF:

0.00273

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00751

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00492

AC:

1236

AN:

251336

Hom.:

AF XY:

0.00502

AC XY:

682

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00214

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.00266

Gnomad SAS exome

AF:

0.00340

Gnomad FIN exome

AF:

0.00259

Gnomad NFE exome

AF:

0.00792

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00682

AC:

9976

AN:

1461742

Hom.:

Cov.:

AF XY:

0.00668

AC XY:

4859

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.00197

Gnomad4 ASJ exome

AF:

0.000842

Gnomad4 EAS exome

AF:

0.00161

Gnomad4 SAS exome

AF:

0.00335

Gnomad4 FIN exome

AF:

0.00360

Gnomad4 NFE exome

AF:

0.00800

Gnomad4 OTH exome

AF:

0.00555

GnomAD4 genome

AF:

0.00451

AC:

687

AN:

152332

Hom.:

Cov.:

AF XY:

0.00422

AC XY:

314

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00152

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00173

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.00273

Gnomad4 NFE

AF:

0.00751

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00575

Hom.:

Bravo

AF:

0.00422

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.00774

EpiControl

AF:

0.00693

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	Labcorp Genetics (formerly Invitae), Labcorp	Jun 06, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

6.3

DANN

Benign

0.68

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