Variant 2-241191245-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001370694.2(ANO7):c.160C>T(p.Arg54Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000164 in 1,613,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R54Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

ANO7
NM_001370694.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.207

Variant links:

Genes affected

ANO7 (HGNC:31677): (anoctamin 7) This prostate-specific gene encodes a cytoplasmic protein, as well as a polytopic membrane protein which may serve as a target in prostate cancer diagnosis and immunotherapy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2011]

ANO7 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09140876).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO7	NM_001370694.2 linkuse as main transcript	c.160C>T	p.Arg54Trp	missense_variant	3/25	ENST00000674324.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO7	ENST00000674324.2 linkuse as main transcript	c.160C>T	p.Arg54Trp	missense_variant	3/25		NM_001370694.2	A2
ANO7	ENST00000274979.12 linkuse as main transcript	c.322C>T	p.Arg108Trp	missense_variant	3/25	1		P2	Q6IWH7-1
ANO7	ENST00000402530.8 linkuse as main transcript	c.160C>T	p.Arg54Trp	missense_variant	3/4	1
ANO7	ENST00000402430.8 linkuse as main transcript	c.160C>T	p.Arg54Trp	missense_variant	3/22	5

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000956

AC:

AN:

250988

Hom.:

AF XY:

0.0000958

AC XY:

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000203

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000166

AC:

243

AN:

1461480

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

118

AN XY:

727078

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000205

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000145

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000200

Hom.:

Bravo

AF:

0.000181

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000415

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

Jul 21, 2021

The c.322C>T (p.R108W) alteration is located in exon 3 (coding exon 3) of the ANO7 gene. This alteration results from a C to T substitution at nucleotide position 322, causing the arginine (R) at amino acid position 108 to be replaced by a tryptophan (W). 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

0.088

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.23

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.52

T;T;T

M_CAP

Benign

0.048

MetaRNN

Benign

0.091

T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.55

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-4.2

D;N;D

REVEL

Benign

0.16

Sift

Uncertain

0.012

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.0040

B;D;.

Vest4

0.23

MVP

0.40

MPC

0.29

ClinPred

0.23

GERP RS

-0.24

Varity_R

0.18

gMVP

0.42

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