rs144158336

chr13-37002475-CAT-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_181503.3(EXOSC8):c.55-10_55-9del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00302 in 1,519,264 control chromosomes in the GnomAD database, including 106 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (48 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (58 hom.)
• Consequence: EXOSC8 NM_181503.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.35

Genes affected

EXOSC8 (HGNC:17035): (exosome component 8) This gene encodes a 3'-5' exoribonuclease that specifically interacts with mRNAs containing AU-rich elements. The encoded protein is part of the exosome complex that is important for the degradation of numerous RNA species. A pseudogene of this gene is found on chromosome 6. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 13-37002475-CAT-C is Benign according to our data. Variant chr13-37002475-CAT-C is described in ClinVar as [Likely_benign]. Clinvar id is 235309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOSC8	NM_181503.3	c.55-10_55-9del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000389704.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOSC8	ENST00000389704.4	c.55-10_55-9del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_181503.3	P1

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2404 AN: 152034 Hom.: 48 Cov.: 32

Gnomad AFR AF: 0.0554

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00497

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00413 AC: 932 AN: 225694 Hom.: 29 AF XY: 0.00310 AC XY: 382 AN XY: 123204

Gnomad AFR exome AF: 0.0581

Gnomad AMR exome AF: 0.00181

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000122

Gnomad SAS exome AF: 0.000151

Gnomad FIN exome AF: 0.0000483

Gnomad NFE exome AF: 0.0000764

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.00160 AC: 2183 AN: 1367112 Hom.: 58 AF XY: 0.00146 AC XY: 997 AN XY: 681922

Gnomad4 AFR exome AF: 0.0605

Gnomad4 AMR exome AF: 0.00215

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000518

Gnomad4 SAS exome AF: 0.000158

Gnomad4 FIN exome AF: 0.0000388

Gnomad4 NFE exome AF: 0.0000765

Gnomad4 OTH exome AF: 0.00304

GnomAD4 genome AF: 0.0158 AC: 2409 AN: 152152 Hom.: 48 Cov.: 32 AF XY: 0.0156 AC XY: 1161 AN XY: 74388

Gnomad4 AFR AF: 0.0554

Gnomad4 AMR AF: 0.00497

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00771 Hom.: 6

Bravo AF: 0.0178

Asia WGS AF: 0.00260 AC: 9 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Feb 11, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 26, 2024	- -

Pontocerebellar hypoplasia, type 1C Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jan 13, 2022

- -

Computational scores

Source: dbNSFP v4.3

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: rs144158336; hg19: chr13-37576612;