Variant 3-43372837-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001204831.3(ANO10):c.1808G>A(p.Cys603Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000888 in 1,535,384 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00048 ( 4 hom. )

Consequence

ANO10
NM_001204831.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.31

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 links:

SNRK (HGNC:):

SNRK links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004222065).

BP6

Variant 3-43372837-C-T is Benign according to our data. Variant chr3-43372837-C-T is described in ClinVar as [Benign]. Clinvar id is 446832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0046 (701/152334) while in subpopulation AFR AF= 0.0162 (674/41576). AF 95% confidence interval is 0.0152. There are 3 homozygotes in gnomad4. There are 313 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO10	NM_018075.5 linkuse as main transcript	c.1915-5863G>A		intron_variant		ENST00000292246.8	NP_060545.3	Q9NW15-1A0A024R2S0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO10	ENST00000292246.8 linkuse as main transcript	c.1915-5863G>A		intron_variant		1	NM_018075.5	ENSP00000292246.3		Q9NW15-1

Frequencies

GnomAD3 genomes

AF:

0.00457

AC:

695

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0161

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

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:

0.00

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000756

AC:

AN:

128366

Hom.:

AF XY:

0.000697

AC XY:

AN XY:

70300

show subpopulations

Gnomad AFR exome

AF:

0.0138

Gnomad AMR exome

AF:

0.000534

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000479

AC:

662

AN:

1383050

Hom.:

Cov.:

AF XY:

0.000419

AC XY:

286

AN XY:

682374

show subpopulations

Gnomad4 AFR exome

AF:

0.0178

Gnomad4 AMR exome

AF:

0.000869

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000505

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000927

Gnomad4 OTH exome

AF:

0.000881

GnomAD4 genome

AF:

0.00460

AC:

701

AN:

152334

Hom.:

Cov.:

AF XY:

0.00420

AC XY:

313

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0162

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00244

Hom.:

Bravo

AF:

0.00560

ExAC

AF:

0.000207

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 21, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

2.2

DANN

Benign

0.75

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.20

MetaRNN

Benign

0.0042

MetaSVM

Benign

-1.0

PROVEAN

Benign

0.35

REVEL

Benign

0.12

Sift

Benign

0.23

Sift4G

Benign

0.76

Vest4

0.17

MVP

0.24

ClinPred

0.0076

GERP RS

2.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over