2-241191245-C-T

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 (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

ANO7
NM_001370694.2 missense

Scores

1
4
14

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]

Genome browser will be placed here

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 Protein UniProt
ANO7NM_001370694.2 linkuse as main transcriptc.160C>T p.Arg54Trp 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.160C>T p.Arg54Trp missense_variant 3/25 NM_001370694.2 ENSP00000501393 A2
ANO7ENST00000274979.12 linkuse as main transcriptc.322C>T p.Arg108Trp missense_variant 3/251 ENSP00000274979 P2Q6IWH7-1
ANO7ENST00000402530.8 linkuse as main transcriptc.160C>T p.Arg54Trp missense_variant 3/41 ENSP00000383985
ANO7ENST00000402430.8 linkuse as main transcriptc.160C>T p.Arg54Trp missense_variant 3/225 ENSP00000385418

Frequencies

GnomAD3 genomes
AF:
0.000145
AC:
22
AN:
152208
Hom.:
0
Cov.:
33
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:
24
AN:
250988
Hom.:
0
AF XY:
0.0000958
AC XY:
13
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.:
0
Cov.:
32
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:
22
AN:
152208
Hom.:
0
Cov.:
33
AF XY:
0.000148
AC XY:
11
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.:
0
Bravo
AF:
0.000181
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000698
AC:
6
ExAC
AF:
0.000115
AC:
14
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 submitterclinical testingAmbry GeneticsJul 21, 2021The 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
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
15
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.44
.;T;.
Eigen
Benign
-0.72
Eigen_PC
Benign
-0.91
FATHMM_MKL
Benign
0.028
N
LIST_S2
Benign
0.52
T;T;T
M_CAP
Benign
0.048
D
MetaRNN
Benign
0.091
T;T;T
MetaSVM
Benign
-0.80
T
MutationAssessor
Benign
0.55
N;N;N
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.38
T
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
T
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.

Other links and lift over

dbSNP: rs138809031; hg19: chr2-242130660; API