3-43366474-C-T

Variant names:

• chr3-43366474-C-T
• rs17075612
• NM_018075.5:c.*432G>A

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.*432G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000621 in 161,032 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: ANO10 NM_018075.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• 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=-0.92).

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.*432G>A		3_prime_UTR	Exon 13 of 13	NP_060545.3
	ANO10	NM_001346464.2		c.*432G>A		3_prime_UTR	Exon 14 of 14	NP_001333393.1
	ANO10	NM_001346467.2		c.*432G>A		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.*432G>A		3_prime_UTR	Exon 13 of 13	ENSP00000292246.3	Q9NW15-1
	ANO10	ENST00000350459.8	TSL:1	c.*432G>A		3_prime_UTR	Exon 12 of 12	ENSP00000327767.4	Q9NW15-2
	ANO10	ENST00000970566.1		c.*432G>A		3_prime_UTR	Exon 15 of 15	ENSP00000640625.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000621 AC: 1 AN: 161032 Hom.: 0 Cov.: 0 AF XY: 0.0000117 AC XY: 1 AN XY: 85716

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 5198

American (AMR) AF: 0.00 AC: 0 AN: 7536

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4074

East Asian (EAS) AF: 0.00 AC: 0 AN: 7496

South Asian (SAS) AF: 0.0000364 AC: 1 AN: 27486

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7660

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 588

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 92802

Other (OTH) AF: 0.00 AC: 0 AN: 8192

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.19
DANN	Benign	0.42
PhyloP100		-1.4

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: rs17075612; hg19: chr3-43407966;