3-43576988-T-A

Position:

• chr3-43576988-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018075.5(ANO10):​c.866A>T​(p.His289Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANO10 NM_018075.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.25

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO10	NM_018075.5	c.866A>T	p.His289Leu	missense_variant	6/13	ENST00000292246.8	NP_060545.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO10	ENST00000292246.8	c.866A>T	p.His289Leu	missense_variant	6/13	1	NM_018075.5	ENSP00000292246.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251122 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135700

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.23	T;.;.;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.062	D
MetaRNN	Uncertain	0.63	D;D;D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.2	M;.;M;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-5.0	D;D;D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0050	D;T;D;T
Sift4G	Benign	0.49	T;T;T;T
Polyphen		0.98	D;D;.;D
Vest4		0.72
MutPred		0.43		Loss of disorder (P = 0.0508);.;Loss of disorder (P = 0.0508);.;
MVP		0.81
MPC		0.46
ClinPred		0.97	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.76
gMVP		0.86

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: rs371063079; hg19: chr3-43618480;