Variant 11-420756-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001012302.3(ANO9):c.1595T>A(p.Val532Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,454,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ANO9
NM_001012302.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.81

Variant links:

Genes affected

ANO9 (HGNC:20679): (anoctamin 9) The protein encoded by this gene is a member of the TMEM16 (anoctamin) family of proteins, some of which form integral membrane calcium-activated chloride channels. The function of the encoded protein has yet to be elucidated, although it may have channel-forming abilities and also may have phospholipid scramblase activity. This gene has been observed to be upregulated in stage II and III colorectal cancers. [provided by RefSeq, Dec 2016]

ANO9 links:

ANO9 (HGNC:):

ANO9 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.9

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO9	NM_001012302.3 linkuse as main transcript	c.1595T>A	p.Val532Asp	missense_variant	18/23	ENST00000332826.7	NP_001012302.2	A1A5B4-1
ANO9	NM_001347882.2 linkuse as main transcript	c.1163T>A	p.Val388Asp	missense_variant	17/22		NP_001334811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO9	ENST00000332826.7 linkuse as main transcript	c.1595T>A	p.Val532Asp	missense_variant	18/23	1	NM_001012302.3	ENSP00000332788.6		A1A5B4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1454392

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

723500

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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

Jun 05, 2024

The c.1595T>A (p.V532D) alteration is located in exon 18 (coding exon 18) of the ANO9 gene. This alteration results from a T to A substitution at nucleotide position 1595, causing the valine (V) at amino acid position 532 to be replaced by an aspartic acid (D). 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

0.69

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.32

Eigen

Benign

0.17

Eigen_PC

Benign

0.030

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.49

MetaRNN

Pathogenic

0.90

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.3

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-5.3

REVEL

Uncertain

0.41

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.054

Polyphen

0.99

Vest4

0.68

MutPred

0.68

Gain of relative solvent accessibility (P = 0.0166);

MVP

0.47

MPC

1.1

ClinPred

0.97

GERP RS

3.7

Varity_R

0.26

gMVP

0.86

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