3-43366474-C-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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]

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

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO10	NM_018075.5	MANE Select	c.*432G>T		3_prime_UTR	Exon 13 of 13	NP_060545.3
	ANO10	NM_001346464.2		c.*432G>T		3_prime_UTR	Exon 14 of 14	NP_001333393.1
	ANO10	NM_001346467.2		c.*432G>T		3_prime_UTR	Exon 14 of 14	NP_001333396.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO10	ENST00000292246.8	TSL:1 MANE Select	c.*432G>T		3_prime_UTR	Exon 13 of 13	ENSP00000292246.3	Q9NW15-1
	ANO10	ENST00000350459.8	TSL:1	c.*432G>T		3_prime_UTR	Exon 12 of 12	ENSP00000327767.4	Q9NW15-2
	ANO10	ENST00000970566.1		c.*432G>T		3_prime_UTR	Exon 15 of 15	ENSP00000640625.1

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

African (AFR) AF: 0.158 AC: 823 AN: 5194

American (AMR) AF: 0.0183 AC: 138 AN: 7534

Ashkenazi Jewish (ASJ) AF: 0.00761 AC: 31 AN: 4074

East Asian (EAS) AF: 0.00 AC: 0 AN: 7496

South Asian (SAS) AF: 0.00364 AC: 100 AN: 27484

European-Finnish (FIN) AF: 0.00196 AC: 15 AN: 7660

Middle Eastern (MID) AF: 0.0289 AC: 17 AN: 588

European-Non Finnish (NFE) AF: 0.00674 AC: 625 AN: 92796

Other (OTH) AF: 0.0148 AC: 121 AN: 8186

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

African (AFR) AF: 0.160 AC: 6626 AN: 41538

American (AMR) AF: 0.0348 AC: 532 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4824

European-Finnish (FIN) AF: 0.000941 AC: 10 AN: 10626

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00698 AC: 475 AN: 68042

Other (OTH) AF: 0.0440 AC: 93 AN: 2114

Alfa AF: 0.0316 Hom.: 118

Bravo AF: 0.0589

Asia WGS AF: 0.0130 AC: 47 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal recessive spinocerebellar ataxia 10 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.53
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs17075612; hg19: chr3-43407966;