4-121801447-A-G

Variant names:

• chr4-121801447-A-G
• NM_005033.3:c.23A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005033.3(EXOSC9):​c.23A>G​(p.Asn8Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: EXOSC9 NM_005033.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.18

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3118918).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOSC9	NM_005033.3	c.23A>G	p.Asn8Ser	missense_variant	Exon 1 of 12	ENST00000243498.10	NP_005024.2
EXOSC9	NM_001034194.2	c.23A>G	p.Asn8Ser	missense_variant	Exon 1 of 13		NP_001029366.1
EXOSC9	XM_011532035.4	c.23A>G	p.Asn8Ser	missense_variant	Exon 1 of 11		XP_011530337.1
EXOSC9	XR_007057929.1	n.125A>G		non_coding_transcript_exon_variant	Exon 1 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOSC9	ENST00000243498.10	c.23A>G	p.Asn8Ser	missense_variant	Exon 1 of 12	1	NM_005033.3	ENSP00000243498.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.028	T;.;.
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M;M;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Benign	0.086
Sift	Benign	0.19	T;T;T
Sift4G	Benign	0.37	T;T;T
Polyphen		0.75	P;B;.
Vest4		0.62
MutPred		0.24		Gain of glycosylation at T4 (P = 0.0252);Gain of glycosylation at T4 (P = 0.0252);Gain of glycosylation at T4 (P = 0.0252);
MVP		0.26
MPC		0.063
ClinPred		0.93	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.65
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-122722602;