dbSNP rs138000380: ANO10:p.Asp615Asn (chr3-43432682-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018075.5(ANO10):c.1843G>A(p.Asp615Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000492 in 1,613,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00050 ( 0 hom. )

Consequence

ANO10
NM_018075.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:8B:2

Conservation

PhyloP100: 7.15

Publications

19 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2106108).

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.1843G>A	p.Asp615Asn	missense	Exon 12 of 13	NP_060545.3
ANO10	NM_001346464.2		c.1960G>A	p.Asp654Asn	missense	Exon 13 of 14	NP_001333393.1
ANO10	NM_001346467.2		c.1960G>A	p.Asp654Asn	missense	Exon 13 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.1843G>A	p.Asp615Asn	missense	Exon 12 of 13	ENSP00000292246.3	Q9NW15-1
ANO10	ENST00000350459.8	TSL:1	c.1273G>A	p.Asp425Asn	missense	Exon 11 of 12	ENSP00000327767.4	Q9NW15-2
ANO10	ENST00000970566.1		c.1996G>A	p.Asp666Asn	missense	Exon 14 of 15	ENSP00000640625.1

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000407

AC:

102

AN:

250800

AF XY:

0.000428

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00547

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000344

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000503

AC:

735

AN:

1461664

Hom.:

Cov.:

AF XY:

0.000499

AC XY:

363

AN XY:

727146

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33474

American (AMR)

AF:

0.0000224

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00532

AC:

139

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39654

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.000150

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000490

AC:

545

AN:

1111890

Other (OTH)

AF:

0.000679

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

110

147

184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000388

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41550

American (AMR)

AF:

0.000327

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0000944

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000500

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000524

Hom.:

Bravo

AF:

0.000336

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000346

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000593

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal recessive spinocerebellar ataxia 10 (4)

not provided (4)

not specified (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.21

MetaSVM

Uncertain

0.053

MutationAssessor

Pathogenic

3.5

PhyloP100

7.2

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-4.6

REVEL

Pathogenic

0.84

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.012

Polyphen

0.81

Vest4

0.94

MVP

0.77

MPC

0.37

ClinPred

0.89

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.82

gMVP

0.86

Mutation Taster

=4/96

disease causing (ClinVar)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over