Variant 11-70088074-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018043.7(ANO1):c.431G>C(p.Arg144Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000987 in 1,317,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0000085 ( 0 hom. )

Consequence

ANO1
NM_018043.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0360

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 links:

ANO1 (HGNC:):

ANO1 links:

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ACMG classification

Classification made for transcript

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=0.109253824).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO1	NM_018043.7 linkuse as main transcript	c.431G>C	p.Arg144Pro	missense_variant	2/26	ENST00000355303.10	NP_060513.5	Q5XXA6-1Q9NW72

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO1	ENST00000355303.10 linkuse as main transcript	c.431G>C	p.Arg144Pro	missense_variant	2/26	1	NM_018043.7	ENSP00000347454.5		Q5XXA6-1

Frequencies

GnomAD3 genomes

AF:

0.0000207

AC:

AN:

145200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000366

AC:

AN:

54600

Hom.:

AF XY:

0.00

AC XY:

AN XY:

27118

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000383

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000853

AC:

AN:

1172346

Hom.:

Cov.:

AF XY:

0.00000710

AC XY:

AN XY:

563714

show subpopulations

Gnomad4 AFR exome

AF:

0.0000827

Gnomad4 AMR exome

AF:

0.000382

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000314

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000207

AC:

AN:

145200

Hom.:

Cov.:

AF XY:

0.0000142

AC XY:

AN XY:

70500

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000151

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

ExAC

AF:

0.0000366

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2023

The c.431G>C (p.R144P) alteration is located in exon 2 (coding exon 2) of the ANO1 gene. This alteration results from a G to C substitution at nucleotide position 431, causing the arginine (R) at amino acid position 144 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.43

T;.;.;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.34

LIST_S2

Uncertain

0.88

D;D;D;D

M_CAP

Benign

0.055

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.3

M;.;.;.

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.8

D;D;D;D

REVEL

Benign

0.23

Sift

Benign

0.079

T;D;D;T

Sift4G

Benign

0.089

T;D;T;T

Polyphen

0.64

P;.;D;.

Vest4

0.52

MutPred

0.38

Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);.;.;

MVP

0.75

MPC

0.87

ClinPred

0.70

GERP RS

1.1

Varity_R

0.67

gMVP

0.80

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over