NM_005033.3:c.66+51A>C

Variant names:

• chr4-121801541-A-C
• rs57880593
• NM_005033.3:c.66+51A>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005033.3(EXOSC9):​c.66+51A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00285 in 1,568,876 control chromosomes in the GnomAD database, including 133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (72 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (61 hom.)
• Consequence: EXOSC9 NM_005033.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.25

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 4-121801541-A-C is Benign according to our data. Variant chr4-121801541-A-C is described in ClinVar as [Benign]. Clinvar id is 1179427.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOSC9	NM_005033.3	c.66+51A>C		intron_variant	Intron 1 of 11	ENST00000243498.10	NP_005024.2
EXOSC9	NM_001034194.2	c.66+51A>C		intron_variant	Intron 1 of 12		NP_001029366.1
EXOSC9	XM_011532035.4	c.66+51A>C		intron_variant	Intron 1 of 10		XP_011530337.1
EXOSC9	XR_007057929.1	n.168+51A>C		intron_variant	Intron 1 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOSC9	ENST00000243498.10	c.66+51A>C		intron_variant	Intron 1 of 11	1	NM_005033.3	ENSP00000243498.5

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2225 AN: 152190 Hom.: 71 Cov.: 33

Gnomad AFR AF: 0.0513

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00957

GnomAD3 exomes AF: 0.00364 AC: 911 AN: 250240 Hom.: 25 AF XY: 0.00273 AC XY: 370 AN XY: 135464

Gnomad AFR exome AF: 0.0497

Gnomad AMR exome AF: 0.00237

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000142

Gnomad OTH exome AF: 0.000982

GnomAD4 exome AF: 0.00158 AC: 2239 AN: 1416568 Hom.: 61 Cov.: 24 AF XY: 0.00139 AC XY: 986 AN XY: 707370

Gnomad4 AFR exome AF: 0.0552

Gnomad4 AMR exome AF: 0.00244

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000141

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000925

Gnomad4 OTH exome AF: 0.00331

GnomAD4 genome AF: 0.0147 AC: 2235 AN: 152308 Hom.: 72 Cov.: 33 AF XY: 0.0141 AC XY: 1052 AN XY: 74490

Gnomad4 AFR AF: 0.0514

Gnomad4 AMR AF: 0.00405

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00947

Alfa AF: 0.00803 Hom.: 5

Bravo AF: 0.0164

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 21, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.17
DANN	Benign	0.64

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

Other links and lift over

dbSNP: rs57880593; hg19: chr4-122722696;