Genetic Variant ANO10:p.Asp45LysfsTer13 (chr3-43605720-C-CTT) – ACMG Classification: Pathogenic (12 pts)

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_018075.5(ANO10):c.131_132dupAA(p.Asp45LysfsTer13) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ANO10
NM_018075.5 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 1.09

Publications

0 publications found

Variant links:

Genes affected

ANO10 (HGNC:25519): (anoctamin 10) The transmembrane protein encoded by this gene belongs to the anoctamin family of calcium-activated chloride channels, also known as the transmembrane 16 family. The encoded protein contains eight transmembrane domains with cytosolic N- and C-termini. Defects in this gene may cause autosomal recessive spinocerebellar ataxia-10. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

ANO10 Gene-Disease associations (from GenCC):

autosomal recessive spinocerebellar ataxia 10
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ANO10 links:

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ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 12 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 3-43605720-C-CTT is Pathogenic according to our data. Variant chr3-43605720-C-CTT is described in ClinVar as Pathogenic. ClinVar VariationId is 1335511.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018075.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ANO10	NM_018075.5	MANE Select	c.131_132dupAA	p.Asp45LysfsTer13	frameshift	Exon 2 of 13	NP_060545.3
ANO10	NM_001346464.2		c.131_132dupAA	p.Asp45LysfsTer13	frameshift	Exon 2 of 14	NP_001333393.1
ANO10	NM_001346467.2		c.131_132dupAA	p.Asp45LysfsTer13	frameshift	Exon 2 of 14	NP_001333396.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANO10	ENST00000292246.8	TSL:1 MANE Select	c.131_132dupAA	p.Asp45LysfsTer13	frameshift	Exon 2 of 13	ENSP00000292246.3	Q9NW15-1
ANO10	ENST00000350459.8	TSL:1	c.131_132dupAA	p.Asp45LysfsTer13	frameshift	Exon 2 of 12	ENSP00000327767.4	Q9NW15-2
ANO10	ENST00000970566.1		c.131_132dupAA	p.Asp45LysfsTer13	frameshift	Exon 2 of 15	ENSP00000640625.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1437176

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715350

African (AFR)

AF:

0.00

AC:

AN:

32854

American (AMR)

AF:

0.00

AC:

AN:

44076

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25506

East Asian (EAS)

AF:

0.00

AC:

AN:

38580

South Asian (SAS)

AF:

0.00

AC:

AN:

85596

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52176

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5682

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1093640

Other (OTH)

AF:

0.00

AC:

AN:

59066

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Pathogenic

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over