3-43366727-G-A

Variant names:

• chr3-43366727-G-A
• rs111871863
• NM_018075.5:c.*179C>T

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.*179C>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 0.0218 in 676,920 control chromosomes in the GnomAD database, including 229 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 0.018 (39 hom., cov: 32)
  • Exomes 𝑓: 0.023 (190 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: -1.67
• Publications: 3 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=-0.86).
• BP6: Variant 3-43366727-G-A is Benign according to our data. Variant chr3-43366727-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 345171.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.018 (2748/152288) while in subpopulation NFE AF = 0.0311 (2117/68010). AF 95% confidence interval is 0.03. There are 39 homozygotes in GnomAd4. There are 1302 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 39 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.*179C>T		3_prime_UTR	Exon 13 of 13	NP_060545.3
	ANO10	NM_001346464.2		c.*179C>T		3_prime_UTR	Exon 14 of 14	NP_001333393.1
	ANO10	NM_001346467.2		c.*179C>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.*179C>T		3_prime_UTR	Exon 13 of 13	ENSP00000292246.3	Q9NW15-1
	ANO10	ENST00000350459.8	TSL:1	c.*179C>T		3_prime_UTR	Exon 12 of 12	ENSP00000327767.4	Q9NW15-2
	ANO10	ENST00000970566.1		c.*179C>T		3_prime_UTR	Exon 15 of 15	ENSP00000640625.1

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2749 AN: 152170 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.00552

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.00942

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.0149

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0311

Gnomad OTH AF: 0.00910

GnomAD4 exome AF: 0.0229 AC: 12009 AN: 524632 Hom.: 190 Cov.: 6 AF XY: 0.0223 AC XY: 6237 AN XY: 279618

African (AFR) AF: 0.00563 AC: 84 AN: 14924

American (AMR) AF: 0.0115 AC: 353 AN: 30806

Ashkenazi Jewish (ASJ) AF: 0.00414 AC: 70 AN: 16916

East Asian (EAS) AF: 0.0000634 AC: 2 AN: 31558

South Asian (SAS) AF: 0.0116 AC: 639 AN: 55246

European-Finnish (FIN) AF: 0.0203 AC: 662 AN: 32684

Middle Eastern (MID) AF: 0.00894 AC: 20 AN: 2236

European-Non Finnish (NFE) AF: 0.0311 AC: 9691 AN: 311354

Other (OTH) AF: 0.0169 AC: 488 AN: 28908

GnomAD4 genome AF: 0.0180 AC: 2748 AN: 152288 Hom.: 39 Cov.: 32 AF XY: 0.0175 AC XY: 1302 AN XY: 74462

African (AFR) AF: 0.00551 AC: 229 AN: 41574

American (AMR) AF: 0.00941 AC: 144 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.0114 AC: 55 AN: 4826

European-Finnish (FIN) AF: 0.0149 AC: 158 AN: 10626

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0311 AC: 2117 AN: 68010

Other (OTH) AF: 0.00900 AC: 19 AN: 2110

Alfa AF: 0.0281 Hom.: 20

Bravo AF: 0.0166

Asia WGS AF: 0.00635 AC: 22 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	-0.86
CADD	Benign	0.64
DANN	Benign	0.81
PhyloP100		-1.7
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: rs111871863; hg19: chr3-43408219;