3-43372790-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_018075.5(ANO10):c.1915-5816C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,511,604 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (4 hom.)
• Consequence: ANO10 NM_018075.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.363

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

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0049410462).
• BP6: Variant 3-43372790-G-T is Benign according to our data. Variant chr3-43372790-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 425294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00204 (311/152330) while in subpopulation NFE AF= 0.00245 (167/68036). AF 95% confidence interval is 0.00215. There are 1 homozygotes in gnomad4. There are 171 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO10	NM_018075.5	c.1915-5816C>A		intron_variant		ENST00000292246.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO10	ENST00000292246.8	c.1915-5816C>A		intron_variant		1	NM_018075.5	P1

Frequencies

GnomAD3 genomes AF: 0.00204 AC: 311 AN: 152212 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00867

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00245

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00167 AC: 214 AN: 128382 Hom.: 0 AF XY: 0.00174 AC XY: 122 AN XY: 70302

Gnomad AFR exome AF: 0.000328

Gnomad AMR exome AF: 0.000698

Gnomad ASJ exome AF: 0.00235

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00928

Gnomad NFE exome AF: 0.00239

Gnomad OTH exome AF: 0.00300

GnomAD4 exome AF: 0.00214 AC: 2914 AN: 1359274 Hom.: 4 Cov.: 25 AF XY: 0.00211 AC XY: 1419 AN XY: 672112

Gnomad4 AFR exome AF: 0.000354

Gnomad4 AMR exome AF: 0.000561

Gnomad4 ASJ exome AF: 0.00272

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00732

Gnomad4 NFE exome AF: 0.00235

Gnomad4 OTH exome AF: 0.00159

GnomAD4 genome AF: 0.00204 AC: 311 AN: 152330 Hom.: 1 Cov.: 32 AF XY: 0.00230 AC XY: 171 AN XY: 74478

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.000980

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00867

Gnomad4 NFE AF: 0.00245

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00132 Hom.: 0

Bravo AF: 0.00121

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00285 AC: 11

ExAC AF: 0.000251 AC: 4

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2023	ANO10: BP4, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 02, 2020	- -

ANO10-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 08, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	0.35
Dann	Benign	0.85
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.0070	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.098
Sift	Pathogenic	0.0	D
Vest4		0.092
MVP		0.39
ClinPred		0.026	T
GERP RS		-1.5

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

Publications

LitVar

Other links and lift over

dbSNP: rs146629436; hg19: chr3-43414282;