chr1-11072581-G-T

Position:

• chr1-11072581-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001998.3(EXOSC10):​c.2158-410C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 172,080 control chromosomes in the GnomAD database, including 36,046 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 (31107 hom., cov: 33)
  • Exomes 𝑓: 0.69 (4939 hom.)
• Consequence: EXOSC10 NM_001001998.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83

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]

ENSG00000226849 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• 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.2158-410C>A		intron_variant		ENST00000376936.9	NP_001001998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOSC10	ENST00000376936.9	c.2158-410C>A		intron_variant		1	NM_001001998.3	ENSP00000366135.4

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91871 AN: 152022 Hom.: 31093 Cov.: 33

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.636

GnomAD4 exome AF: 0.694 AC: 13833 AN: 19940 Hom.: 4939 Cov.: 0 AF XY: 0.691 AC XY: 7402 AN XY: 10712

Gnomad4 AFR exome AF: 0.187

Gnomad4 AMR exome AF: 0.735

Gnomad4 ASJ exome AF: 0.523

Gnomad4 EAS exome AF: 0.711

Gnomad4 SAS exome AF: 0.694

Gnomad4 FIN exome AF: 0.639

Gnomad4 NFE exome AF: 0.716

Gnomad4 OTH exome AF: 0.646

GnomAD4 genome AF: 0.604 AC: 91906 AN: 152140 Hom.: 31107 Cov.: 33 AF XY: 0.608 AC XY: 45226 AN XY: 74374

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.732

Gnomad4 ASJ AF: 0.593

Gnomad4 EAS AF: 0.786

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.718

Gnomad4 NFE AF: 0.738

Gnomad4 OTH AF: 0.638

Alfa AF: 0.621 Hom.: 3574

Bravo AF: 0.591

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.12
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2791648; hg19: chr1-11132638;