rs144158336

Variant names:

• chr13-37002475-CAT-C
• rs144158336
• NM_181503.3:c.55-10_55-9delAT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_181503.3(EXOSC8):​c.55-10_55-9delAT variant causes a 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 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.35
• Publications: 0 publications found

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]

EXOSC8 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia, type 1C

  Inheritance: AR, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
• pontocerebellar hypoplasia type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181503.3. 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
	EXOSC8	NM_181503.3	MANE Select	c.55-10_55-9delAT		intron	N/A	NP_852480.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOSC8	ENST00000389704.4	TSL:1 MANE Select	c.55-10_55-9delAT		intron	N/A	ENSP00000374354.3
	EXOSC8	ENST00000490537.6	TSL:1	n.74-10_74-9delAT		intron	N/A
	EXOSC8	ENST00000488108.6	TSL:4	n.1699_1700delAT		non_coding_transcript_exon	Exon 1 of 2

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

GnomAD2 exomes AF: 0.00413 AC: 932 AN: 225694 AF XY: 0.00310

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 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

African (AFR) AF: 0.0605 AC: 1829 AN: 30242

American (AMR) AF: 0.00215 AC: 82 AN: 38106

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24246

East Asian (EAS) AF: 0.0000518 AC: 2 AN: 38620

South Asian (SAS) AF: 0.000158 AC: 12 AN: 76190

European-Finnish (FIN) AF: 0.0000388 AC: 2 AN: 51610

Middle Eastern (MID) AF: 0.000750 AC: 4 AN: 5336

European-Non Finnish (NFE) AF: 0.0000765 AC: 80 AN: 1046214

Other (OTH) AF: 0.00304 AC: 172 AN: 56548

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

African (AFR) AF: 0.0554 AC: 2299 AN: 41494

American (AMR) AF: 0.00497 AC: 76 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68002

Other (OTH) AF: 0.0104 AC: 22 AN: 2112

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

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 11, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Pontocerebellar hypoplasia, type 1C Benign:1

Jan 13, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3
Mutation Taster		=100/0	polymorphism

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: rs144158336; hg19: chr13-37576612;