rs755987255

Variant names:

• chr4-121801887-T-A
• NM_005033.3:c.127T>A

Your query was ambiguous. Multiple possible variants found:

• chr4-121801887-T-A
• chr4-121801887-T-C
• chr4-121801887-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005033.3(EXOSC9):​c.127T>A​(p.Tyr43Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,626 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EXOSC9 NM_005033.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.23

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOSC9	NM_005033.3	c.127T>A	p.Tyr43Asn	missense_variant	Exon 2 of 12	ENST00000243498.10	NP_005024.2
EXOSC9	NM_001034194.2	c.127T>A	p.Tyr43Asn	missense_variant	Exon 2 of 13		NP_001029366.1
EXOSC9	XM_011532035.4	c.127T>A	p.Tyr43Asn	missense_variant	Exon 2 of 11		XP_011530337.1
EXOSC9	XR_007057929.1	n.229T>A		non_coding_transcript_exon_variant	Exon 2 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOSC9	ENST00000243498.10	c.127T>A	p.Tyr43Asn	missense_variant	Exon 2 of 12	1	NM_005033.3	ENSP00000243498.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461626 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727146

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	26
DANN	Benign	0.97
DEOGEN2	Benign	0.20	T;.;.;T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.67	D;D;D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.1	L;L;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-4.6	D;D;D;D
REVEL	Benign	0.29
Sift	Benign	0.059	T;D;D;T
Sift4G	Benign	0.16	T;T;T;T
Polyphen		0.98	D;B;.;D
Vest4		0.85
MutPred		0.49		Gain of glycosylation at T41 (P = 0.112);Gain of glycosylation at T41 (P = 0.112);Gain of glycosylation at T41 (P = 0.112);.;
MVP		0.61
MPC		0.11
ClinPred		0.97	D
GERP RS		5.6
Varity_R		0.58
gMVP		0.65

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: chr4-122723042;