chr3-43366459-C-T

Variant names:

• chr3-43366459-C-T
• rs112787589
• NM_018075.5:c.*447G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_018075.5(ANO10):​c.*447G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00755 in 295,332 control chromosomes in the GnomAD database, including 14 homozygotes. 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 0.0070 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0082 (6 hom.)
• Consequence: ANO10 NM_018075.5 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -3.09
• Publications: 1 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-43366459-C-T is Benign according to our data. Variant chr3-43366459-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 345163.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00695 (1059/152298) while in subpopulation NFE AF = 0.0116 (792/68016). AF 95% confidence interval is 0.011. There are 8 homozygotes in GnomAd4. There are 512 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

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.*447G>A		3_prime_UTR	Exon 13 of 13	NP_060545.3
	ANO10	NM_001346464.2		c.*447G>A		3_prime_UTR	Exon 14 of 14	NP_001333393.1
	ANO10	NM_001346467.2		c.*447G>A		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.*447G>A		3_prime_UTR	Exon 13 of 13	ENSP00000292246.3	Q9NW15-1
	ANO10	ENST00000350459.8	TSL:1	c.*447G>A		3_prime_UTR	Exon 12 of 12	ENSP00000327767.4	Q9NW15-2
	ANO10	ENST00000970566.1		c.*447G>A		3_prime_UTR	Exon 15 of 15	ENSP00000640625.1

Frequencies

GnomAD3 genomes AF: 0.00696 AC: 1059 AN: 152180 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00399

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00791

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.00573

GnomAD4 exome AF: 0.00819 AC: 1171 AN: 143034 Hom.: 6 Cov.: 0 AF XY: 0.00756 AC XY: 574 AN XY: 75930

African (AFR) AF: 0.00101 AC: 5 AN: 4936

American (AMR) AF: 0.00424 AC: 28 AN: 6608

Ashkenazi Jewish (ASJ) AF: 0.00758 AC: 27 AN: 3560

East Asian (EAS) AF: 0.00 AC: 0 AN: 6842

South Asian (SAS) AF: 0.00219 AC: 52 AN: 23772

European-Finnish (FIN) AF: 0.00976 AC: 67 AN: 6868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 536

European-Non Finnish (NFE) AF: 0.0112 AC: 923 AN: 82622

Other (OTH) AF: 0.00947 AC: 69 AN: 7290

GnomAD4 genome AF: 0.00695 AC: 1059 AN: 152298 Hom.: 8 Cov.: 32 AF XY: 0.00688 AC XY: 512 AN XY: 74470

African (AFR) AF: 0.00176 AC: 73 AN: 41566

American (AMR) AF: 0.00399 AC: 61 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00720 AC: 25 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4832

European-Finnish (FIN) AF: 0.00791 AC: 84 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0116 AC: 792 AN: 68016

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.00837 Hom.: 0

Bravo AF: 0.00642

Asia WGS AF: 0.000866 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	-	Autosomal recessive spinocerebellar ataxia 10 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.17
DANN	Benign	0.55
PhyloP100		-3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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: rs112787589; hg19: chr3-43407951;