NM_018075.5:c.473-4411C>T

Variant names:

• chr3-43584883-G-A
• rs1013758
• NM_018075.5:c.473-4411C>T

Variant summary

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

The NM_018075.5(ANO10):​c.473-4411C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 151,922 control chromosomes in the GnomAD database, including 17,825 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 0.44 (17825 hom., cov: 31)
• Consequence: ANO10 NM_018075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.436
• Publications: 8 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO10	NM_018075.5	c.473-4411C>T		intron_variant	Intron 4 of 12	ENST00000292246.8	NP_060545.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO10	ENST00000292246.8	c.473-4411C>T		intron_variant	Intron 4 of 12	1	NM_018075.5	ENSP00000292246.3

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66750 AN: 151804 Hom.: 17829 Cov.: 31

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.439 AC: 66749 AN: 151922 Hom.: 17825 Cov.: 31 AF XY: 0.445 AC XY: 33028 AN XY: 74258

African (AFR) AF: 0.139 AC: 5774 AN: 41428

American (AMR) AF: 0.381 AC: 5816 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1716 AN: 3472

East Asian (EAS) AF: 0.767 AC: 3953 AN: 5152

South Asian (SAS) AF: 0.629 AC: 3022 AN: 4808

European-Finnish (FIN) AF: 0.596 AC: 6278 AN: 10542

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.567 AC: 38526 AN: 67952

Other (OTH) AF: 0.466 AC: 980 AN: 2102

Alfa AF: 0.522 Hom.: 13396

Bravo AF: 0.404

Asia WGS AF: 0.665 AC: 2312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.7
DANN	Benign	0.61
PhyloP100		0.44
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: rs1013758; hg19: chr3-43626375;