2-240691975-C-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_198998.3(AQP12A):​c.62C>A​(p.Ala21Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000529 in 1,588,622 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000047 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000053 ( 4 hom. )

Consequence

AQP12A
NM_198998.3 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.174
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 Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.38100088).
BS2
High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AQP12ANM_198998.3 linkc.62C>A p.Ala21Asp 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.62C>A p.Ala21Asp missense_variant Exon 1 of 4 1 NM_198998.3 ENSP00000337144.4 Q8IXF9

Frequencies

GnomAD3 genomes
AF:
0.0000472
AC:
7
AN:
148290
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.000104
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000371
AC:
9
AN:
242804
Hom.:
1
AF XY:
0.0000378
AC XY:
5
AN XY:
132324
show subpopulations
Gnomad AFR exome
AF:
0.000195
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:
0.0000535
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000535
AC:
77
AN:
1440332
Hom.:
4
Cov.:
81
AF XY:
0.0000600
AC XY:
43
AN XY:
716808
show subpopulations
Gnomad4 AFR exome
AF:
0.0000304
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000617
Gnomad4 OTH exome
AF:
0.000134
GnomAD4 genome
AF:
0.0000472
AC:
7
AN:
148290
Hom.:
0
Cov.:
32
AF XY:
0.0000830
AC XY:
6
AN XY:
72248
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.000104
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000828
Hom.:
0
Bravo
AF:
0.0000567
ESP6500AA
AF:
0.000461
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000502
AC:
6
EpiCase
AF:
0.0000549
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 20, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.62C>A (p.A21D) alteration is located in exon 1 (coding exon 1) of the AQP12A gene. This alteration results from a C to A substitution at nucleotide position 62, causing the alanine (A) at amino acid position 21 to be replaced by an aspartic acid (D). 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
Pathogenic
0.67
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
17
DANN
Benign
0.96
DEOGEN2
Uncertain
0.59
D;.
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.59
D
LIST_S2
Benign
0.63
T;T
M_CAP
Benign
0.0051
T
MetaRNN
Benign
0.38
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.2
M;.
PrimateAI
Uncertain
0.71
T
PROVEAN
Uncertain
-2.9
D;D
REVEL
Benign
0.15
Sift
Benign
0.15
T;T
Sift4G
Benign
0.071
T;T
Polyphen
0.26
B;.
Vest4
0.60
MVP
0.30
MPC
0.68
ClinPred
0.084
T
GERP RS
1.5
Varity_R
0.16
gMVP
0.82

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: rs145322760; hg19: chr2-241631392; API