3-43516593-T-C

Variant names:

• chr3-43516593-T-C
• rs737516
• NM_018075.5:c.1797+33127A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018075.5(ANO10):​c.1797+33127A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,022 control chromosomes in the GnomAD database, including 20,671 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 0.49 (20671 hom., cov: 32)
• Consequence: ANO10 NM_018075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.722
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO10	NM_018075.5	c.1797+33127A>G		intron_variant	Intron 11 of 12	ENST00000292246.8	NP_060545.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO10	ENST00000292246.8	c.1797+33127A>G		intron_variant	Intron 11 of 12	1	NM_018075.5	ENSP00000292246.3

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75088 AN: 151904 Hom.: 20660 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.494 AC: 75129 AN: 152022 Hom.: 20671 Cov.: 32 AF XY: 0.501 AC XY: 37195 AN XY: 74310

African (AFR) AF: 0.250 AC: 10359 AN: 41484

American (AMR) AF: 0.555 AC: 8473 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1751 AN: 3470

East Asian (EAS) AF: 0.828 AC: 4278 AN: 5168

South Asian (SAS) AF: 0.649 AC: 3129 AN: 4820

European-Finnish (FIN) AF: 0.599 AC: 6316 AN: 10542

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39039 AN: 67950

Other (OTH) AF: 0.519 AC: 1095 AN: 2110

Alfa AF: 0.551 Hom.: 15088

Bravo AF: 0.480

Asia WGS AF: 0.714 AC: 2482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.72
PhyloP100		-0.72
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: rs737516; hg19: chr3-43558085;