2-240691972-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_198998.3(AQP12A):​c.59C>T​(p.Ala20Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,588,952 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 12 hom. )

Consequence

AQP12A
NM_198998.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.17
Variant links:
Genes affected
AQP12A (HGNC:19941): (aquaporin 12A) Predicted to enable channel activity. Predicted to be involved in transmembrane transport. Predicted to be integral component of membrane. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.03139028).
BS2
High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AQP12ANM_198998.3 linkc.59C>T p.Ala20Val missense_variant Exon 1 of 4 ENST00000337801.9 NP_945349.1 Q8IXF9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AQP12AENST00000337801.9 linkc.59C>T p.Ala20Val missense_variant Exon 1 of 4 1 NM_198998.3 ENSP00000337144.4 Q8IXF9

Frequencies

GnomAD3 genomes
AF:
0.000108
AC:
16
AN:
148302
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000248
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000892
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000107
AC:
26
AN:
242868
Hom.:
1
AF XY:
0.000136
AC XY:
18
AN XY:
132358
show subpopulations
Gnomad AFR exome
AF:
0.000325
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000200
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000134
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000119
AC:
172
AN:
1440650
Hom.:
12
Cov.:
60
AF XY:
0.000121
AC XY:
87
AN XY:
716950
show subpopulations
Gnomad4 AFR exome
AF:
0.0000911
Gnomad4 AMR exome
AF:
0.000101
Gnomad4 ASJ exome
AF:
0.0000384
Gnomad4 EAS exome
AF:
0.000531
Gnomad4 SAS exome
AF:
0.000154
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000113
Gnomad4 OTH exome
AF:
0.000101
GnomAD4 genome
AF:
0.000108
AC:
16
AN:
148302
Hom.:
1
Cov.:
32
AF XY:
0.000111
AC XY:
8
AN XY:
72248
show subpopulations
Gnomad4 AFR
AF:
0.000248
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000892
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000119
Hom.:
1
ESP6500AA
AF:
0.000459
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000125
AC:
15
EpiCase
AF:
0.0000549
EpiControl
AF:
0.000179

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 21, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.59C>T (p.A20V) alteration is located in exon 1 (coding exon 1) of the AQP12A gene. This alteration results from a C to T substitution at nucleotide position 59, causing the alanine (A) at amino acid position 20 to be replaced by a valine (V). 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
0.079
BayesDel_addAF
Benign
-0.59
T
BayesDel_noAF
Benign
-0.78
CADD
Benign
0.15
DANN
Benign
0.87
DEOGEN2
Benign
0.030
T;.
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.014
N
LIST_S2
Benign
0.49
T;T
M_CAP
Benign
0.0032
T
MetaRNN
Benign
0.031
T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.66
N;.
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
0.020
N;N
REVEL
Benign
0.015
Sift
Benign
0.57
T;T
Sift4G
Benign
0.37
T;T
Polyphen
0.0030
B;.
Vest4
0.12
MVP
0.040
MPC
0.34
ClinPred
0.0056
T
GERP RS
-3.2
Varity_R
0.019
gMVP
0.29

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: rs141084461; hg19: chr2-241631389; API