rs34104729

Variant names:

• chr3-43688476-A-G
• rs34104729
• NM_001346468.2:c.-12+3041T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001346468.2(ANO10):​c.-12+3041T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 152,276 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.030 (86 hom., cov: 32)
• Consequence: ANO10 NM_001346468.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340
• 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]

ANO10 Gene-Disease associations (from GenCC):

• autosomal recessive spinocerebellar ataxia 10

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0295 (4494/152276) while in subpopulation NFE AF = 0.0393 (2673/68004). AF 95% confidence interval is 0.0381. There are 86 homozygotes in GnomAd4. There are 2173 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 86 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346468.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO10	NM_001346468.2		c.-12+3041T>C		intron	N/A	NP_001333397.1
	ANO10	NM_001346469.2		c.-12+3041T>C		intron	N/A	NP_001333398.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO10	ENST00000413397.5	TSL:4	c.-12+3041T>C		intron	N/A	ENSP00000399103.1
	ANO10	ENST00000439141.5	TSL:4	c.-106+3041T>C		intron	N/A	ENSP00000397360.1
	ANO10	ENST00000428831.1	TSL:5	c.-106+2139T>C		intron	N/A	ENSP00000406712.1

Frequencies

GnomAD3 genomes AF: 0.0295 AC: 4496 AN: 152158 Hom.: 86 Cov.: 32

Gnomad AFR AF: 0.00755

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0263

Gnomad ASJ AF: 0.0853

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0196

Gnomad FIN AF: 0.0545

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0393

Gnomad OTH AF: 0.0340

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0295 AC: 4494 AN: 152276 Hom.: 86 Cov.: 32 AF XY: 0.0292 AC XY: 2173 AN XY: 74470

African (AFR) AF: 0.00755 AC: 314 AN: 41568

American (AMR) AF: 0.0263 AC: 402 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0853 AC: 296 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.0192 AC: 93 AN: 4832

European-Finnish (FIN) AF: 0.0545 AC: 578 AN: 10612

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0393 AC: 2673 AN: 68004

Other (OTH) AF: 0.0336 AC: 71 AN: 2110

Alfa AF: 0.0363 Hom.: 16

Bravo AF: 0.0266

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.97
PhyloP100		0.34

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34104729; hg19: chr3-43729968;