chr3-43476675-T-G

Variant names:

• chr3-43476675-T-G
• rs1351631
• NM_018075.5:c.1798-43948A>C

Variant summary

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

The NM_018075.5(ANO10):​c.1798-43948A>C 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 151,986 control chromosomes in the GnomAD database, including 20,641 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 (20641 hom., cov: 32)
• Consequence: ANO10 NM_018075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540
• 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]

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO10	NM_018075.5	MANE Select	c.1798-43948A>C		intron	N/A	NP_060545.3
	ANO10	NM_001346464.2		c.1915-43948A>C		intron	N/A	NP_001333393.1
	ANO10	NM_001346467.2		c.1915-43948A>C		intron	N/A	NP_001333396.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO10	ENST00000292246.8	TSL:1 MANE Select	c.1798-43948A>C		intron	N/A	ENSP00000292246.3
	ANO10	ENST00000350459.8	TSL:1	c.1228-43948A>C		intron	N/A	ENSP00000327767.4
	ANO10	ENST00000414522.6	TSL:2	c.1797+73045A>C		intron	N/A	ENSP00000396990.2

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75025 AN: 151868 Hom.: 20633 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.494 AC: 75064 AN: 151986 Hom.: 20641 Cov.: 32 AF XY: 0.500 AC XY: 37173 AN XY: 74300

African (AFR) AF: 0.249 AC: 10324 AN: 41460

American (AMR) AF: 0.554 AC: 8449 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1748 AN: 3468

East Asian (EAS) AF: 0.826 AC: 4275 AN: 5176

South Asian (SAS) AF: 0.649 AC: 3127 AN: 4818

European-Finnish (FIN) AF: 0.599 AC: 6304 AN: 10532

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

European-Non Finnish (NFE) AF: 0.575 AC: 39057 AN: 67962

Other (OTH) AF: 0.518 AC: 1095 AN: 2112

Alfa AF: 0.544 Hom.: 12316

Bravo AF: 0.480

Asia WGS AF: 0.714 AC: 2481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.2
DANN	Benign	0.82
PhyloP100		-0.054
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: rs1351631; hg19: chr3-43518167;