dbSNP rs367921445: ANO9:p.Val675Leu (chr11-418901-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001012302.3(ANO9):c.2023G>C(p.Val675Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V675M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ANO9
NM_001012302.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.889

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09228799).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012302.3. 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
	ANO9	NM_001012302.3	MANE Select	c.2023G>C	p.Val675Leu	missense	Exon 21 of 23	NP_001012302.2	A1A5B4-1
	ANO9	NM_001347882.2		c.1591G>C	p.Val531Leu	missense	Exon 20 of 22	NP_001334811.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANO9	ENST00000332826.7	TSL:1 MANE Select	c.2023G>C	p.Val675Leu	missense	Exon 21 of 23	ENSP00000332788.6	A1A5B4-1
ANO9	ENST00000524802.1	TSL:1	n.515G>C		non_coding_transcript_exon	Exon 1 of 3
ANO9	ENST00000528927.5	TSL:1	n.2134G>C		non_coding_transcript_exon	Exon 20 of 22

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461376

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726958

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53004

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111938

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.054

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.58

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.092

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

0.89

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.99

REVEL

Benign

0.091

Sift

Benign

0.61

Sift4G

Benign

0.25

Polyphen

0.31

Vest4

0.26

MutPred

0.51

Loss of sheet (P = 0.0817)

MVP

0.20

MPC

0.38

ClinPred

0.084

GERP RS

-0.021

Varity_R

0.029

gMVP

0.64

Mutation Taster

=92/8

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