dbSNP rs1336423150: ANO8:p.Gln1186Pro (chr19-17323659-T-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020959.3(ANO8):c.3557A>C(p.Gln1186Pro) 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. Q1186H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0 ( 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: 0.336

Publications

1 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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.027379483).

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.3557A>C	p.Gln1186Pro	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.3557A>C	p.Gln1186Pro	missense	Exon 18 of 18	ENSP00000159087.4	Q9HCE9-1
ANO8	ENST00000597643.5	TSL:2	n.*2369A>C		non_coding_transcript_exon	Exon 18 of 18	ENSP00000469751.1	M0QYD2
ANO8	ENST00000597643.5	TSL:2	n.*2369A>C		3_prime_UTR	Exon 18 of 18	ENSP00000469751.1	M0QYD2

Frequencies

GnomAD3 genomes

AF:

0.000490

AC:

AN:

2040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00633

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

55666

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

25736

African (AFR)

AF:

0.00

AC:

AN:

1140

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

346

East Asian (EAS)

AF:

0.00

AC:

AN:

336

South Asian (SAS)

AF:

0.00

AC:

AN:

1130

European-Finnish (FIN)

AF:

0.00

AC:

AN:

276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

50456

Other (OTH)

AF:

0.00

AC:

AN:

1810

GnomAD4 genome

AF:

0.000490

AC:

AN:

2040

Hom.:

Cov.:

AF XY:

0.000906

AC XY:

AN XY:

1104

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

538

American (AMR)

AF:

0.00633

AC:

AN:

158

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

108

South Asian (SAS)

AF:

0.00

AC:

AN:

130

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

932

Other (OTH)

AF:

0.00

AC:

AN:

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00644

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

0.053

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.041

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.32

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

0.34

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.37

REVEL

Benign

0.012

Sift

Benign

0.24

Sift4G

Benign

0.28

Polyphen

0.26

Vest4

0.19

MVP

0.16

ClinPred

0.14

GERP RS

2.9

Varity_R

0.072

gMVP

0.085

Mutation Taster

=95/5

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over