Genetic Variant ANO8:p.Ala1170Thr (chr19-17323708-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020959.3(ANO8):c.3508G>A(p.Ala1170Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1170D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ANO8
NM_020959.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.870

Publications

0 publications found

Variant links:

Genes affected

ANO8 (HGNC:29329): (anoctamin 8) Enables intracellular calcium activated chloride channel activity. Involved in chloride transport. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ANO8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07857558).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020959.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO8	NM_020959.3	MANE Select	c.3508G>A	p.Ala1170Thr	missense	Exon 18 of 18	NP_066010.1	Q9HCE9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANO8	ENST00000159087.7	TSL:1 MANE Select	c.3508G>A	p.Ala1170Thr	missense	Exon 18 of 18	ENSP00000159087.4	Q9HCE9-1
ANO8	ENST00000597643.5	TSL:2	n.*2320G>A		non_coding_transcript_exon	Exon 18 of 18	ENSP00000469751.1	M0QYD2
ANO8	ENST00000597643.5	TSL:2	n.*2320G>A		3_prime_UTR	Exon 18 of 18	ENSP00000469751.1	M0QYD2

Frequencies

GnomAD3 genomes

AF:

0.00000670

AC:

AN:

149158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000194

AC:

AN:

1033384

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

487836

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21132

American (AMR)

AF:

0.00

AC:

AN:

7132

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12340

East Asian (EAS)

AF:

0.00

AC:

AN:

23612

South Asian (SAS)

AF:

0.00

AC:

AN:

19082

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2682

European-Non Finnish (NFE)

AF:

0.00000112

AC:

AN:

889836

Other (OTH)

AF:

0.0000249

AC:

AN:

40220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000670

AC:

AN:

149158

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72664

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40844

American (AMR)

AF:

0.00

AC:

AN:

15034

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3430

East Asian (EAS)

AF:

0.00

AC:

AN:

5100

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9718

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

66962

Other (OTH)

AF:

0.00

AC:

AN:

2040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000843

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.9

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.046

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.40

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.079

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.20

PhyloP100

-0.87

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.58

REVEL

Benign

0.066

Sift

Benign

0.19

Sift4G

Benign

0.23

Polyphen

0.0

Vest4

0.054

MutPred

0.18

Gain of glycosylation at A1170 (P = 0.0036)

MVP

0.27

ClinPred

0.070

GERP RS

-3.2

Varity_R

0.043

gMVP

0.082

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over