16-70251509-T-C

Variant names:

• chr16-70251509-T-C
• NM_058219.3:c.392A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_058219.3(EXOSC6):​c.392A>G​(p.Glu131Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EXOSC6 NM_058219.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.790
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.392A>G	p.Glu131Gly	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.392A>G	p.Glu131Gly	missense	Exon 1 of 1	ENSP00000398597.1	Q5RKV6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1125592 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 544844

African (AFR) AF: 0.00 AC: 0 AN: 22788

American (AMR) AF: 0.00 AC: 0 AN: 13044

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15656

East Asian (EAS) AF: 0.00 AC: 0 AN: 23778

South Asian (SAS) AF: 0.00 AC: 0 AN: 38462

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23668

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2990

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 941154

Other (OTH) AF: 0.00 AC: 0 AN: 44052

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.025
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.58	T
M_CAP	Pathogenic	0.87	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.79
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.21
Sift	Uncertain	0.018	D
Sift4G	Benign	0.10	T
Polyphen		0.99	D
Vest4		0.21
MutPred		0.49		Loss of stability (P = 0.0449)
MVP		0.87
MPC		1.7
ClinPred		0.68	D
GERP RS		2.5
PromoterAI		-0.0055	Neutral
Varity_R		0.40
gMVP		0.36

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

Other links and lift over

hg19: chr16-70285412;