NM_018075.5:c.*569T>C

Variant names:

• chr3-43366337-A-G
• rs1044107285
• NM_018075.5:c.*569T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018075.5(ANO10):​c.*569T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000656 in 152,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANO10 NM_018075.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.111
• Publications: 0 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]

SNRK (HGNC:30598): (SNF related kinase) SNRK is a member of the sucrose nonfermenting (SNF)-related kinase family of serine/threonine kinases (Kertesz et al., 2002 [PubMed 12234663]).[supplied by OMIM, Apr 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO10	NM_018075.5	MANE Select	c.*569T>C		3_prime_UTR	Exon 13 of 13	NP_060545.3
	ANO10	NM_001346464.2		c.*569T>C		3_prime_UTR	Exon 14 of 14	NP_001333393.1
	ANO10	NM_001346467.2		c.*569T>C		3_prime_UTR	Exon 14 of 14	NP_001333396.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO10	ENST00000292246.8	TSL:1 MANE Select	c.*569T>C		3_prime_UTR	Exon 13 of 13	ENSP00000292246.3	Q9NW15-1
	ANO10	ENST00000920383.1		c.*569T>C		splice_region	Exon 14 of 14	ENSP00000590442.1
	ANO10	ENST00000910688.1		c.*569T>C		splice_region	Exon 14 of 14	ENSP00000580747.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 22868 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 11912

African (AFR) AF: 0.00 AC: 0 AN: 684

American (AMR) AF: 0.00 AC: 0 AN: 3210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 324

East Asian (EAS) AF: 0.00 AC: 0 AN: 1750

South Asian (SAS) AF: 0.00 AC: 0 AN: 2866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 42

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 12476

Other (OTH) AF: 0.00 AC: 0 AN: 1048

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152336 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74496

African (AFR) AF: 0.0000241 AC: 1 AN: 41576

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Autosomal recessive spinocerebellar ataxia 10 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.3
DANN	Benign	0.53
PhyloP100		-0.11

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: rs1044107285; hg19: chr3-43407829;