Variant chr3-43366462-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018075.5(ANO10):c.*444C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 296,838 control chromosomes in the GnomAD database, including 192 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.026 ( 169 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 23 hom. )

Consequence

ANO10
NM_018075.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.59

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:30598): (SNF related kinase) SNRK is a member of the sucrose nonfermenting (SNF)-related kinase family of serine/threonine kinases (Kertesz et al., 2002 [PubMed 12234663]).[supplied by OMIM, Apr 2009]

SNRK links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 3-43366462-G-A is Benign according to our data. Variant chr3-43366462-G-A is described in ClinVar as [Benign]. Clinvar id is 345164.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO10	NM_018075.5 linkuse as main transcript	c.*444C>T		3_prime_UTR_variant	13/13	ENST00000292246.8

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO10	ENST00000292246.8 linkuse as main transcript	c.*444C>T	3_prime_UTR_variant	13/13	1	NM_018075.5	P1	Q9NW15-1
ANO10	ENST00000350459.8 linkuse as main transcript	c.*444C>T	3_prime_UTR_variant	12/12	1			Q9NW15-2
ANO10	ENST00000396091.7 linkuse as main transcript	c.*444C>T	3_prime_UTR_variant	12/12	2			Q9NW15-3
SNRK	ENST00000468628.2 linkuse as main transcript	n.230+4594G>A	intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0255

AC:

3879

AN:

152174

Hom.:

169

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0873

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0102

Gnomad ASJ

AF:

0.00577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.0163

GnomAD4 exome

AF:

0.00412

AC:

596

AN:

144546

Hom.:

Cov.:

AF XY:

0.00338

AC XY:

259

AN XY:

76710

show subpopulations

Gnomad4 AFR exome

AF:

0.0876

Gnomad4 AMR exome

AF:

0.00661

Gnomad4 ASJ exome

AF:

0.00360

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000332

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000610

Gnomad4 OTH exome

AF:

0.00609

GnomAD4 genome

AF:

0.0255

AC:

3885

AN:

152292

Hom.:

169

Cov.:

AF XY:

0.0247

AC XY:

1842

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0872

Gnomad4 AMR

AF:

0.0102

Gnomad4 ASJ

AF:

0.00577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000720

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0118

Hom.:

Bravo

AF:

0.0286

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Autosomal recessive spinocerebellar ataxia 10

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.23

DANN

Benign

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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