rs1318348

Variant names:

• chr1-11070361-A-G
• rs1318348
• NM_001001998.3:c.2316+539T>C

Variant summary

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

The NM_001001998.3(EXOSC10):​c.2316+539T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 150,684 control chromosomes in the GnomAD database, including 30,736 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 (30736 hom., cov: 25)
• Consequence: EXOSC10 NM_001001998.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.805
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001998.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOSC10	NM_001001998.3	MANE Select	c.2316+539T>C		intron	N/A	NP_001001998.1
	EXOSC10	NM_002685.4		c.2241+539T>C		intron	N/A	NP_002676.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOSC10	ENST00000376936.9	TSL:1 MANE Select	c.2316+539T>C		intron	N/A	ENSP00000366135.4
	EXOSC10	ENST00000304457.11	TSL:1	c.2241+539T>C		intron	N/A	ENSP00000307307.7
	EXOSC10-AS1	ENST00000452378.1	TSL:2	n.244-298A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.604 AC: 90874 AN: 150570 Hom.: 30722 Cov.: 25

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.688

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.635

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.603 AC: 90909 AN: 150684 Hom.: 30736 Cov.: 25 AF XY: 0.607 AC XY: 44593 AN XY: 73490

African (AFR) AF: 0.266 AC: 10937 AN: 41040

American (AMR) AF: 0.730 AC: 11007 AN: 15084

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2017 AN: 3464

East Asian (EAS) AF: 0.786 AC: 4013 AN: 5108

South Asian (SAS) AF: 0.717 AC: 3392 AN: 4734

European-Finnish (FIN) AF: 0.715 AC: 7323 AN: 10244

Middle Eastern (MID) AF: 0.700 AC: 203 AN: 290

European-Non Finnish (NFE) AF: 0.738 AC: 49972 AN: 67718

Other (OTH) AF: 0.638 AC: 1334 AN: 2092

Alfa AF: 0.640 Hom.: 4400

Bravo AF: 0.589

Asia WGS AF: 0.732 AC: 2547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.2
DANN	Benign	0.39
PhyloP100		0.81
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: rs1318348; hg19: chr1-11130418;