Variant 19-17323734-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_020959.3(ANO8):c.3482G>T(p.Gly1161Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,204,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

ANO8
NM_020959.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.254

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:

ANO8 (HGNC:):

ANO8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08593598).

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO8	NM_020959.3 linkuse as main transcript	c.3482G>T	p.Gly1161Val	missense_variant	18/18	ENST00000159087.7	NP_066010.1	Q9HCE9-1
ANO8	XR_936199.4 linkuse as main transcript	n.4331G>T		non_coding_transcript_exon_variant	18/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ANO8	ENST00000159087.7 linkuse as main transcript	c.3482G>T	p.Gly1161Val	missense_variant	18/18	1	NM_020959.3	ENSP00000159087.4	Q9HCE9-1
ANO8	ENST00000597643.5 linkuse as main transcript	n.*2294G>T		non_coding_transcript_exon_variant	18/18	2		ENSP00000469751.1	M0QYD2
ANO8	ENST00000597643.5 linkuse as main transcript	n.*2294G>T		3_prime_UTR_variant	18/18	2		ENSP00000469751.1	M0QYD2

Frequencies

GnomAD3 genomes

AF:

0.0000531

AC:

AN:

150680

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:

0.000119

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000225

AC:

237

AN:

1054086

Hom.:

Cov.:

AF XY:

0.000223

AC XY:

111

AN XY:

497634

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000995

Gnomad4 NFE exome

AF:

0.000253

Gnomad4 OTH exome

AF:

0.000167

GnomAD4 genome

AF:

0.0000531

AC:

AN:

150680

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73492

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000119

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000718

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 01, 2024

The c.3482G>T (p.G1161V) alteration is located in exon 18 (coding exon 18) of the ANO8 gene. This alteration results from a G to T substitution at nucleotide position 3482, causing the glycine (G) at amino acid position 1161 to be replaced by a valine (V). 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

Benign

0.094

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.041

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.45

M_CAP

Pathogenic

0.50

MetaRNN

Benign

0.086

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.69

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.85

REVEL

Benign

0.026

Sift

Uncertain

0.0030

Sift4G

Benign

0.11

Polyphen

0.036

Vest4

0.14

MVP

0.068

ClinPred

0.12

GERP RS

1.7

Varity_R

0.12

gMVP

0.074

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