9-130693804-A-T

Variant names:

• chr9-130693804-A-T
• NM_014285.7:c.13A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014285.7(EXOSC2):​c.13A>T​(p.Met5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,282 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EXOSC2 NM_014285.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17462024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOSC2	NM_014285.7	c.13A>T	p.Met5Leu	missense_variant	Exon 1 of 9	ENST00000372358.10	NP_055100.2
EXOSC2	NM_001282708.1	c.13A>T	p.Met5Leu	missense_variant	Exon 1 of 8		NP_001269637.1
EXOSC2	NM_001282709.1	c.13A>T	p.Met5Leu	missense_variant	Exon 1 of 8		NP_001269638.1
EXOSC2	NR_104230.1	n.45A>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.13A>T	p.Met5Leu	missense_variant	Exon 1 of 9	1	NM_014285.7	ENSP00000361433.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455282 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 723876

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: 0.00000181

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	0.12
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.012	T;.;T;.;T
Eigen	Benign	-0.011
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.88	D;D;D;D;D
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.17	T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.1	M;M;.;M;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.16	N;N;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.069	T;T;T;T;T
Sift4G	Benign	0.21	T;T;T;T;T
Polyphen		0.0	B;.;.;.;.
Vest4		0.53
MutPred		0.20		Loss of helix (P = 0.028);Loss of helix (P = 0.028);Loss of helix (P = 0.028);Loss of helix (P = 0.028);Loss of helix (P = 0.028);
MVP		0.31
MPC		0.23
ClinPred		0.61	D
GERP RS		6.1
Varity_R		0.69
gMVP		0.46

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: chr9-133569191;