1-11072484-G-C

Variant names:

• chr1-11072484-G-C
• rs2791650
• NM_001001998.3:c.2158-313C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001998.3(EXOSC10):​c.2158-313C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 238,236 control chromosomes in the GnomAD database, including 51,623 homozygotes. 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: 𝑓 0.60 (31086 hom., cov: 32)
  • Exomes 𝑓: 0.68 (20537 hom.)
• Consequence: EXOSC10 NM_001001998.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• Publications: 8 publications found

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]

EXOSC10-AS1 (HGNC:40456): (EXOSC10 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOSC10	NM_001001998.3	c.2158-313C>G		intron_variant	Intron 19 of 24	ENST00000376936.9	NP_001001998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOSC10	ENST00000376936.9	c.2158-313C>G		intron_variant	Intron 19 of 24	1	NM_001001998.3	ENSP00000366135.4

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91800 AN: 151954 Hom.: 31072 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.636

GnomAD4 exome AF: 0.679 AC: 58514 AN: 86162 Hom.: 20537 Cov.: 0 AF XY: 0.681 AC XY: 31231 AN XY: 45868

African (AFR) AF: 0.205 AC: 623 AN: 3040

American (AMR) AF: 0.734 AC: 2951 AN: 4020

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1419 AN: 2666

East Asian (EAS) AF: 0.759 AC: 3127 AN: 4118

South Asian (SAS) AF: 0.685 AC: 7599 AN: 11092

European-Finnish (FIN) AF: 0.647 AC: 2305 AN: 3564

Middle Eastern (MID) AF: 0.601 AC: 196 AN: 326

European-Non Finnish (NFE) AF: 0.707 AC: 37155 AN: 52524

Other (OTH) AF: 0.652 AC: 3139 AN: 4812

GnomAD4 genome AF: 0.604 AC: 91835 AN: 152074 Hom.: 31086 Cov.: 32 AF XY: 0.608 AC XY: 45179 AN XY: 74334

African (AFR) AF: 0.266 AC: 11049 AN: 41484

American (AMR) AF: 0.732 AC: 11182 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2057 AN: 3470

East Asian (EAS) AF: 0.785 AC: 4050 AN: 5156

South Asian (SAS) AF: 0.716 AC: 3457 AN: 4826

European-Finnish (FIN) AF: 0.718 AC: 7579 AN: 10562

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.738 AC: 50195 AN: 67988

Other (OTH) AF: 0.638 AC: 1345 AN: 2108

Alfa AF: 0.563 Hom.: 2071

Bravo AF: 0.590

Asia WGS AF: 0.732 AC: 2548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.41
PhyloP100		0.094
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2791650; hg19: chr1-11132541;