3-43598658-CATT-C

Variant names:

• chr3-43598658-CATT-C
• rs771064874
• NM_018075.5:c.343_345delAAT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PM4_Supporting BS1_Supporting

The NM_018075.5(ANO10):​c.343_345delAAT​(p.Asn115del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.0000854 in 1,603,340 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000074 (1 hom.)
• Consequence: ANO10 NM_018075.5 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00
• Publications: 0 publications found

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: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_018075.5. Strenght limited to Supporting due to length of the change: 1aa.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000197 (30/152066) while in subpopulation AMR AF = 0.00183 (28/15260). AF 95% confidence interval is 0.0013. There are 1 homozygotes in GnomAd4. There are 23 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO10	NM_018075.5	MANE Select	c.343_345delAAT	p.Asn115del	conservative_inframe_deletion	Exon 4 of 13	NP_060545.3
	ANO10	NM_001346464.2		c.343_345delAAT	p.Asn115del	conservative_inframe_deletion	Exon 4 of 14	NP_001333393.1
	ANO10	NM_001346467.2		c.343_345delAAT	p.Asn115del	conservative_inframe_deletion	Exon 4 of 14	NP_001333396.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO10	ENST00000292246.8	TSL:1 MANE Select	c.343_345delAAT	p.Asn115del	conservative_inframe_deletion	Exon 4 of 13	ENSP00000292246.3
	ANO10	ENST00000350459.8	TSL:1	c.343_345delAAT	p.Asn115del	conservative_inframe_deletion	Exon 4 of 12	ENSP00000327767.4
	ANO10	ENST00000414522.6	TSL:2	c.343_345delAAT	p.Asn115del	conservative_inframe_deletion	Exon 4 of 13	ENSP00000396990.2

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152066 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000151 AC: 37 AN: 244254 AF XY: 0.000159

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000829

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000632

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000737 AC: 107 AN: 1451274 Hom.: 1 AF XY: 0.0000804 AC XY: 58 AN XY: 721788

African (AFR) AF: 0.00 AC: 0 AN: 33288

American (AMR) AF: 0.000771 AC: 34 AN: 44120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25888

East Asian (EAS) AF: 0.0000507 AC: 2 AN: 39448

South Asian (SAS) AF: 0.000141 AC: 12 AN: 84820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5584

European-Non Finnish (NFE) AF: 0.0000515 AC: 57 AN: 1105836

Other (OTH) AF: 0.0000333 AC: 2 AN: 60054

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152066 Hom.: 1 Cov.: 32 AF XY: 0.000310 AC XY: 23 AN XY: 74262

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00183 AC: 28 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.000181

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 06, 2017

Athena Diagnostics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.0
Mutation Taster		=72/28	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: rs771064874; hg19: chr3-43640150;