2-241191204-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001370694.2(ANO7):ā€‹c.119A>Cā€‹(p.Gln40Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,613,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.000023 ( 0 hom. )

Consequence

ANO7
NM_001370694.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.06
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.046283215).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ANO7NM_001370694.2 linkuse as main transcriptc.119A>C p.Gln40Pro missense_variant 3/25 ENST00000674324.2 NP_001357623.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ANO7ENST00000674324.2 linkuse as main transcriptc.119A>C p.Gln40Pro missense_variant 3/25 NM_001370694.2 ENSP00000501393 A2
ANO7ENST00000274979.12 linkuse as main transcriptc.281A>C p.Gln94Pro missense_variant 3/251 ENSP00000274979 P2Q6IWH7-1
ANO7ENST00000402530.8 linkuse as main transcriptc.119A>C p.Gln40Pro missense_variant 3/41 ENSP00000383985
ANO7ENST00000402430.8 linkuse as main transcriptc.119A>C p.Gln40Pro missense_variant 3/225 ENSP00000385418

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152198
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251206
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135810
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000145
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:
0.0000176
Gnomad OTH exome
AF:
0.000490
GnomAD4 exome
AF:
0.0000226
AC:
33
AN:
1461594
Hom.:
0
Cov.:
32
AF XY:
0.0000193
AC XY:
14
AN XY:
727138
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
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:
0.0000162
Gnomad4 OTH exome
AF:
0.0000994
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152198
Hom.:
0
Cov.:
33
AF XY:
0.000108
AC XY:
8
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000589
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000761
Hom.:
0
Bravo
AF:
0.000155
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsDec 26, 2023The c.281A>C (p.Q94P) alteration is located in exon 3 (coding exon 3) of the ANO7 gene. This alteration results from a A to C substitution at nucleotide position 281, causing the glutamine (Q) at amino acid position 94 to be replaced by a proline (P). 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
0.062
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
7.3
DANN
Benign
0.46
DEOGEN2
Benign
0.029
.;T;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.031
N
LIST_S2
Benign
0.39
T;T;T
M_CAP
Benign
0.0072
T
MetaRNN
Benign
0.046
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.34
N;N;N
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-1.9
N;N;N
REVEL
Benign
0.095
Sift
Benign
0.22
T;T;T
Sift4G
Uncertain
0.026
D;T;T
Polyphen
0.0
B;B;.
Vest4
0.12
MVP
0.20
MPC
0.13
ClinPred
0.015
T
GERP RS
-2.8
Varity_R
0.099
gMVP
0.18

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs763477706; hg19: chr2-242130619; API