rs2791650

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-11072484-G-A
• chr1-11072484-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001001998.3(EXOSC10):​c.2158-313C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000115 in 86,690 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000115 AC: 1 AN: 86690 Hom.: 0 Cov.: 0 AF XY: 0.0000217 AC XY: 1 AN XY: 46134

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 3052

American (AMR) AF: 0.00 AC: 0 AN: 4034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2680

East Asian (EAS) AF: 0.00 AC: 0 AN: 4136

South Asian (SAS) AF: 0.00 AC: 0 AN: 11142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 330

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 52878

Other (OTH) AF: 0.00 AC: 0 AN: 4836

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2071

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.4
DANN	Benign	0.90
PhyloP100		0.094

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;