rs1318348

Positions:

• chr1-11070361-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOSC10	NM_001001998.3	c.2316+539T>C		intron_variant		ENST00000376936.9	NP_001001998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOSC10	ENST00000376936.9	c.2316+539T>C		intron_variant		1	NM_001001998.3	ENSP00000366135	P1
	ENST00000452378.1	n.244-298A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.786

Gnomad4 SAS AF: 0.717

Gnomad4 FIN AF: 0.715

Gnomad4 NFE AF: 0.738

Gnomad4 OTH AF: 0.638

Alfa AF: 0.655 Hom.: 4367

Bravo AF: 0.589

Asia WGS AF: 0.732 AC: 2547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.2
DANN	Benign	0.39

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

LitVar

Other links and lift over

dbSNP: rs1318348; hg19: chr1-11130418;