Genetic Variant NM_058219.3:c.721G>C (chr16-70251180-C-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6

The NM_058219.3(EXOSC6):c.721G>C(p.Val241Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000073 in 1,370,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

EXOSC6
NM_058219.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.858

Publications

0 publications found

Variant links:

Genes affected

EXOSC6 (HGNC:19055): (exosome component 6) This gene product constitutes one of the subunits of the multisubunit particle called exosome, which mediates mRNA degradation. The composition of human exosome is similar to its yeast counterpart. This protein is homologous to the yeast Mtr3 protein. Its exact function is not known, however, it has been shown using a cell-free RNA decay system that the exosome is required for rapid degradation of unstable mRNAs containing AU-rich elements (AREs), but not for poly(A) shortening. The exosome does not recognize ARE-containing mRNAs on its own, but requires ARE-binding proteins that could interact with the exosome and recruit it to unstable mRNAs, thereby promoting their rapid degradation. [provided by RefSeq, Jul 2008]

EXOSC6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16187462).

BP6

Variant 16-70251180-C-G is Benign according to our data. Variant chr16-70251180-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2681264.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058219.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOSC6	NM_058219.3	MANE Select	c.721G>C	p.Val241Leu	missense	Exon 1 of 1	NP_478126.1	Q5RKV6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOSC6	ENST00000435634.3	TSL:6 MANE Select	c.721G>C	p.Val241Leu	missense	Exon 1 of 1	ENSP00000398597.1	Q5RKV6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.30e-7

AC:

AN:

1370536

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

677708

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28438

American (AMR)

AF:

0.00

AC:

AN:

35030

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24382

East Asian (EAS)

AF:

0.00

AC:

AN:

33052

South Asian (SAS)

AF:

0.00

AC:

AN:

77984

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33974

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4664

European-Non Finnish (NFE)

AF:

9.30e-7

AC:

AN:

1075806

Other (OTH)

AF:

0.00

AC:

AN:

57206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

EBV-positive nodal T- and NK-cell lymphoma (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0053

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.098

LIST_S2

Benign

0.48

M_CAP

Pathogenic

0.52

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.1

PhyloP100

0.86

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.0

REVEL

Benign

0.17

Sift

Benign

0.43

Sift4G

Benign

0.42

Polyphen

0.0

Vest4

0.17

MutPred

0.62

Loss of MoRF binding (P = 0.1289)

MVP

0.74

MPC

0.60

ClinPred

0.11

GERP RS

1.9

Varity_R

0.25

gMVP

0.38

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over