Variant 19-17323540-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_020959.3(ANO8):c.3676T>C(p.Cys1226Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000675 in 1,287,950 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

ANO8
NM_020959.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.588

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO8	NM_020959.3 linkuse as main transcript	c.3676T>C	p.Cys1226Arg	missense_variant	18/18	ENST00000159087.7	NP_066010.1	Q9HCE9-1
ANO8	XR_936199.4 linkuse as main transcript	n.4525T>C		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.3676T>C	p.Cys1226Arg	missense_variant	18/18	1	NM_020959.3	ENSP00000159087.4	Q9HCE9-1
ANO8	ENST00000597643.5 linkuse as main transcript	n.*2488T>C		non_coding_transcript_exon_variant	18/18	2		ENSP00000469751.1	M0QYD2
ANO8	ENST00000597643.5 linkuse as main transcript	n.*2488T>C		3_prime_UTR_variant	18/18	2		ENSP00000469751.1	M0QYD2

Frequencies

GnomAD3 genomes

AF:

0.0000462

AC:

AN:

151564

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000704

AC:

AN:

1136386

Hom.:

Cov.:

AF XY:

0.0000680

AC XY:

AN XY:

544120

show subpopulations

Gnomad4 AFR exome

AF:

0.0000407

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:

0.00

Gnomad4 NFE exome

AF:

0.0000833

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000462

AC:

AN:

151564

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74048

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:

0.000103

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

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

Dec 16, 2022

The c.3676T>C (p.C1226R) alteration is located in exon 18 (coding exon 18) of the ANO8 gene. This alteration results from a T to C substitution at nucleotide position 3676, causing the cysteine (C) at amino acid position 1226 to be replaced by an arginine (R). 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

0.67

BayesDel_addAF

Uncertain

0.028

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.053

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.39

M_CAP

Pathogenic

0.74

MetaRNN

Uncertain

0.70

MetaSVM

Benign

-0.50

MutationAssessor

Benign

0.97

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.2

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.024

Polyphen

0.99

Vest4

0.78

MutPred

0.29

Gain of MoRF binding (P = 0);

MVP

0.13

ClinPred

0.81

GERP RS

3.9

Varity_R

0.91

gMVP

0.089

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