Genetic Variant ANO1:p.Arg81Ser (chr11-70087886-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018043.7(ANO1):c.243G>C(p.Arg81Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R81R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Consequence

ANO1
NM_018043.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.102

Publications

1 publications found

Variant links:

Genes affected

ANO1 (HGNC:21625): (anoctamin 1) Enables calcium activated cation channel activity; intracellular calcium activated chloride channel activity; and iodide transmembrane transporter activity. Involved in cation transport; inorganic anion transport; and positive regulation of insulin secretion involved in cellular response to glucose stimulus. Located in apical plasma membrane and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ANO1 Gene-Disease associations (from GenCC):

moyamoya disease 7
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
intestinal dysmotility syndrome
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

ANO1 links:

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ACMG classification

Classification was made for transcript

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 (MetaRNN=0.063515306).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018043.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANO1	NM_018043.7	MANE Select	c.243G>C	p.Arg81Ser	missense	Exon 2 of 26	NP_060513.5
ANO1	NM_001378092.1		c.366G>C	p.Arg122Ser	missense	Exon 3 of 28	NP_001365021.1	Q5XXA6-5
ANO1	NM_001378093.1		c.243G>C	p.Arg81Ser	missense	Exon 3 of 26	NP_001365022.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANO1	ENST00000355303.10	TSL:1 MANE Select	c.243G>C	p.Arg81Ser	missense	Exon 2 of 26	ENSP00000347454.5	Q5XXA6-1
ANO1	ENST00000531349.6	TSL:1	c.366G>C	p.Arg122Ser	missense	Exon 3 of 28	ENSP00000432843.2	Q5XXA6-5
ANO1	ENST00000930664.1		c.243G>C	p.Arg81Ser	missense	Exon 3 of 26	ENSP00000600723.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000411

AC:

AN:

243144

AF XY:

0.00

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000921

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.089

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.76

M_CAP

Benign

0.020

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

-0.10

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.53

REVEL

Benign

0.023

Sift

Benign

0.54

Sift4G

Benign

0.48

Polyphen

0.0

Vest4

0.14

MutPred

0.38

Gain of glycosylation at R81 (P = 0.0166)

MVP

0.30

MPC

0.49

ClinPred

0.044

GERP RS

0.99

Varity_R

0.11

gMVP

0.51

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over