NM_018075.5:c.*196C>A

Variant names:

• chr3-43366710-G-T
• rs73831274
• NM_018075.5:c.*196C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018075.5(ANO10):​c.*196C>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 0.0092 in 641,070 control chromosomes in the GnomAD database, including 238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (176 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (62 hom.)
• Consequence: ANO10 NM_018075.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.324
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-43366710-G-T is Benign according to our data. Variant chr3-43366710-G-T is described in ClinVar as Benign. ClinVar VariationId is 345170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0846 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO10	NM_018075.5	MANE Select	c.*196C>A		3_prime_UTR	Exon 13 of 13	NP_060545.3
	ANO10	NM_001346464.2		c.*196C>A		3_prime_UTR	Exon 14 of 14	NP_001333393.1
	ANO10	NM_001346467.2		c.*196C>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.*196C>A		3_prime_UTR	Exon 13 of 13	ENSP00000292246.3	Q9NW15-1
	ANO10	ENST00000350459.8	TSL:1	c.*196C>A		3_prime_UTR	Exon 12 of 12	ENSP00000327767.4	Q9NW15-2
	ANO10	ENST00000970566.1		c.*196C>A		3_prime_UTR	Exon 15 of 15	ENSP00000640625.1

Frequencies

GnomAD3 genomes AF: 0.0258 AC: 3922 AN: 152176 Hom.: 175 Cov.: 32

Gnomad AFR AF: 0.0871

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.0206

GnomAD4 exome AF: 0.00403 AC: 1972 AN: 488776 Hom.: 62 Cov.: 5 AF XY: 0.00339 AC XY: 881 AN XY: 260178

African (AFR) AF: 0.0846 AC: 1185 AN: 14000

American (AMR) AF: 0.00635 AC: 179 AN: 28170

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 179 AN: 15550

East Asian (EAS) AF: 0.00 AC: 0 AN: 31206

South Asian (SAS) AF: 0.0000969 AC: 5 AN: 51618

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31032

Middle Eastern (MID) AF: 0.00190 AC: 4 AN: 2106

European-Non Finnish (NFE) AF: 0.000532 AC: 153 AN: 287594

Other (OTH) AF: 0.00971 AC: 267 AN: 27500

GnomAD4 genome AF: 0.0258 AC: 3929 AN: 152294 Hom.: 176 Cov.: 32 AF XY: 0.0247 AC XY: 1840 AN XY: 74470

African (AFR) AF: 0.0870 AC: 3615 AN: 41558

American (AMR) AF: 0.0123 AC: 189 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000632 AC: 43 AN: 68022

Other (OTH) AF: 0.0204 AC: 43 AN: 2108

Alfa AF: 0.00726 Hom.: 13

Bravo AF: 0.0304

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autosomal recessive spinocerebellar ataxia 10 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.50
DANN	Benign	0.84
PhyloP100		0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs73831274; hg19: chr3-43408202;