chr3-43366474-C-A

Variant names:

• chr3-43366474-C-A
• rs17075612
• NM_018075.5:c.*432G>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018075.5(ANO10):​c.*432G>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 0.0308 in 313,322 control chromosomes in the GnomAD database, including 618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.051 (545 hom., cov: 32)
  • Exomes 𝑓: 0.012 (73 hom.)
• Consequence: ANO10 NM_018075.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.35

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-43366474-C-A is Benign according to our data. Variant chr3-43366474-C-A is described in ClinVar as [Benign]. Clinvar id is 345166.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO10	NM_018075.5	c.*432G>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000292246.8	NP_060545.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO10	ENST00000292246	c.*432G>T		3_prime_UTR_variant	Exon 13 of 13	1	NM_018075.5	ENSP00000292246.3
ANO10	ENST00000350459	c.*432G>T		3_prime_UTR_variant	Exon 12 of 12	1		ENSP00000327767.4
ANO10	ENST00000396091	c.*432G>T		3_prime_UTR_variant	Exon 12 of 12	2		ENSP00000379398.3
SNRK	ENST00000468628.2	n.230+4606C>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0511 AC: 7773 AN: 152192 Hom.: 542 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0349

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.000941

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00699

Gnomad OTH AF: 0.0445

GnomAD4 exome AF: 0.0116 AC: 1870 AN: 161012 Hom.: 73 Cov.: 0 AF XY: 0.0104 AC XY: 894 AN XY: 85710

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.0183

Gnomad4 ASJ exome AF: 0.00761

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00364

Gnomad4 FIN exome AF: 0.00196

Gnomad4 NFE exome AF: 0.00674

Gnomad4 OTH exome AF: 0.0148

GnomAD4 genome AF: 0.0511 AC: 7789 AN: 152310 Hom.: 545 Cov.: 32 AF XY: 0.0493 AC XY: 3672 AN XY: 74480

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.0348

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.000941

Gnomad4 NFE AF: 0.00698

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0288 Hom.: 91

Bravo AF: 0.0589

Asia WGS AF: 0.0130 AC: 47 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal recessive spinocerebellar ataxia 10 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.91
CADD	Benign	0.15
DANN	Benign	0.53
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

Other links and lift over

dbSNP: rs17075612; hg19: chr3-43407966;