9-130693855-A-T

Variant names:

• chr9-130693855-A-T
• NM_014285.7:c.64A>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014285.7(EXOSC2):​c.64A>T​(p.Thr22Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EXOSC2 NM_014285.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.636

Genes affected

EXOSC2 (HGNC:17097): (exosome component 2) Predicted to enable RNA binding activity. Involved in positive regulation of cell growth. Located in cytoplasm; nucleolus; and nucleoplasm. Part of nuclear exosome (RNase complex). [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.020805836).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOSC2	NM_014285.7	c.64A>T	p.Thr22Ser	missense_variant	Exon 1 of 9	ENST00000372358.10	NP_055100.2
EXOSC2	NM_001282708.1	c.64A>T	p.Thr22Ser	missense_variant	Exon 1 of 8		NP_001269637.1
EXOSC2	NM_001282709.1	c.64A>T	p.Thr22Ser	missense_variant	Exon 1 of 8		NP_001269638.1
EXOSC2	NR_104230.1	n.96A>T		non_coding_transcript_exon_variant	Exon 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOSC2	ENST00000372358.10	c.64A>T	p.Thr22Ser	missense_variant	Exon 1 of 9	1	NM_014285.7	ENSP00000361433.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460504 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726594

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: 9.00e-7

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	0.068
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.5
DANN	Benign	0.67
DEOGEN2	Benign	0.0091	T;.;T;.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.46	T;T;T;T;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.021	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.28	N;N;.;N;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.44	N;N;N;N;N
REVEL	Benign	0.021
Sift	Benign	0.85	T;T;T;T;T
Sift4G	Benign	0.79	T;T;T;T;T
Polyphen		0.0	B;.;.;.;.
Vest4		0.12
MutPred		0.28		Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);
MVP		0.055
MPC		0.22
ClinPred		0.056	T
GERP RS		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.27

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: chr9-133569242;