3-43561311-C-A

Position:

• chr3-43561311-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018075.5(ANO10):​c.1385G>T​(p.Arg462Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R462Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANO10 NM_018075.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15600681).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO10	NM_018075.5	c.1385G>T	p.Arg462Leu	missense_variant	9/13	ENST00000292246.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO10	ENST00000292246.8	c.1385G>T	p.Arg462Leu	missense_variant	9/13	1	NM_018075.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	T;.;.;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.23	N
LIST_S2	Uncertain	0.92	D;D;D;D;D
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.16	T;T;T;T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	1.8	L;.;.;L;.
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-3.0	D;D;D;D;D
REVEL	Benign	0.14
Sift	Benign	0.064	T;T;D;T;D
Sift4G	Benign	0.21	T;T;T;T;T
Polyphen		0.053	B;P;B;.;B
Vest4		0.22
MutPred		0.54		Loss of loop (P = 0.0203);.;.;Loss of loop (P = 0.0203);.;
MVP		0.18
MPC		0.14
ClinPred		0.22	T
GERP RS		-5.4
Varity_R		0.34
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs3772165; hg19: chr3-43602803;