chr1-11073972-G-C

Position:

• chr1-11073972-G-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.2119C>G​(p.Gln707Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: EXOSC10 NM_001001998.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.35

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=0.22448978).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOSC10	NM_001001998.3	c.2119C>G	p.Gln707Glu	missense_variant	19/25	ENST00000376936.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOSC10	ENST00000376936.9	c.2119C>G	p.Gln707Glu	missense_variant	19/25	1	NM_001001998.3	P1
EXOSC10	ENST00000304457.11	c.2082+259C>G		intron_variant		1
EXOSC10	ENST00000474216.5	n.1356C>G		non_coding_transcript_exon_variant	7/13	2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 27, 2022

The c.2119C>G (p.Q707E) alteration is located in exon 19 (coding exon 19) of the EXOSC10 gene. This alteration results from a C to G substitution at nucleotide position 2119, causing the glutamine (Q) at amino acid position 707 to be replaced by a glutamic acid (E). 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	0.057
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.15
Sift	Benign	0.047	D
Sift4G	Benign	1.0	T
Polyphen		0.69	P
Vest4		0.30
MutPred		0.25		Loss of methylation at K710 (P = 0.0882);
MVP		0.64
MPC		0.24
ClinPred		0.30	T
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: chr1-11134029;