3-43688476-A-G

Position:

• chr3-43688476-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 86 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO10	NM_001346468.2	c.-12+3041T>C		intron_variant			NP_001333397.1
ANO10	NM_001346469.2	c.-12+3041T>C		intron_variant			NP_001333398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO10	ENST00000413397.5	c.-12+3041T>C		intron_variant		4		ENSP00000399103.1
ANO10	ENST00000439141.5	c.-106+3041T>C		intron_variant		4		ENSP00000397360.1
ANO10	ENST00000428831.1	c.-106+2139T>C		intron_variant		5		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

Gnomad4 AFR AF: 0.00755

Gnomad4 AMR AF: 0.0263

Gnomad4 ASJ AF: 0.0853

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0192

Gnomad4 FIN AF: 0.0545

Gnomad4 NFE AF: 0.0393

Gnomad4 OTH AF: 0.0336

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 v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34104729; hg19: chr3-43729968;