1-11074257-C-G

Variant names:

• chr1-11074257-C-G
• NM_001001998.3:c.2056G>C

Variant summary

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

The NM_001001998.3(EXOSC10):​c.2056G>C​(p.Glu686Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: EXOSC10 NM_001001998.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.98

Genes affected

EXOSC10 (HGNC:9138): (exosome component 10) Enables 3'-5'-exoribonuclease activity. Involved in several processes, including RNA catabolic process; maturation of 5.8S rRNA; and negative regulation of telomere maintenance via telomerase. Located in cytosol; nuclear lumen; and transcriptionally active chromatin. 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=0.21053514).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOSC10	NM_001001998.3	c.2056G>C	p.Glu686Gln	missense_variant	Exon 18 of 25	ENST00000376936.9	NP_001001998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOSC10	ENST00000376936.9	c.2056G>C	p.Glu686Gln	missense_variant	Exon 18 of 25	1	NM_001001998.3	ENSP00000366135.4
EXOSC10	ENST00000304457.11	c.2056G>C	p.Glu686Gln	missense_variant	Exon 18 of 24	1		ENSP00000307307.7
EXOSC10	ENST00000474216.5	n.1293G>C		non_coding_transcript_exon_variant	Exon 6 of 13	2
EXOSC10	ENST00000470611.5	n.*31G>C		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2056G>C (p.E686Q) alteration is located in exon 18 (coding exon 18) of the EXOSC10 gene. This alteration results from a G to C substitution at nucleotide position 2056, causing the glutamic acid (E) at amino acid position 686 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.24	.;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.12
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.58	N;N
REVEL	Benign	0.047
Sift	Benign	0.19	T;T
Sift4G	Benign	0.38	T;T
Polyphen		0.12	B;B
Vest4		0.29
MutPred		0.27		Gain of loop (P = 0.002);Gain of loop (P = 0.002);
MVP		0.57
MPC		0.27
ClinPred		0.43	T
GERP RS		3.1
Varity_R		0.22
gMVP		0.30

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: chr1-11134314;