Variant 2-240680382-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001102467.2(AQP12B):c.694G>A(p.Val232Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.00013 ( 0 hom., cov: 14)

Exomes 𝑓: 0.00020 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AQP12B
NM_001102467.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.831

Variant links:

Genes affected

AQP12B (HGNC:6096): (aquaporin 12B) 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]

AQP12B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.040659547).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AQP12B	NM_001102467.2 linkuse as main transcript	c.694G>A	p.Val232Met	missense_variant	2/3	ENST00000407834.4	NP_001095937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AQP12B	ENST00000407834.4 linkuse as main transcript	c.694G>A	p.Val232Met	missense_variant	2/3	1	NM_001102467.2	ENSP00000384894	P2	A6NM10-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

113734

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000313

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000351

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000793

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00971

Gnomad NFE

AF:

0.000115

Gnomad OTH

AF:

0.000732

GnomAD3 exomes

AF:

0.000193

AC:

AN:

88276

Hom.:

AF XY:

0.000225

AC XY:

AN XY:

44454

show subpopulations

Gnomad AFR exome

AF:

0.000156

Gnomad AMR exome

AF:

0.0000631

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000319

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000321

Gnomad OTH exome

AF:

0.000758

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000199

AC:

120

AN:

604258

Hom.:

Cov.:

AF XY:

0.000204

AC XY:

AN XY:

317928

show subpopulations

Gnomad4 AFR exome

AF:

0.000230

Gnomad4 AMR exome

AF:

0.000156

Gnomad4 ASJ exome

AF:

0.000171

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000508

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000170

Gnomad4 OTH exome

AF:

0.000386

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000132

AC:

AN:

113874

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

54136

show subpopulations

Gnomad4 AFR

AF:

0.0000312

Gnomad4 AMR

AF:

0.000350

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000787

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000115

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000965

Hom.:

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

May 24, 2024

The c.694G>A (p.V232M) alteration is located in exon 2 (coding exon 2) of the AQP12B gene. This alteration results from a G to A substitution at nucleotide position 694, causing the valine (V) at amino acid position 232 to be replaced by a methionine (M). 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

0.10

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

4.9

DANN

Benign

0.34

DEOGEN2

Benign

0.20

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.041

T;T

MetaSVM

Benign

-0.75

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.66

.;N

REVEL

Benign

0.11

Sift

Benign

0.13

.;T

Sift4G

Benign

0.18

T;T

Polyphen

0.0040

.;B

Vest4

0.093

MVP

0.22

MPC

0.19

ClinPred

0.011

GERP RS

-0.80

Varity_R

0.030

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.

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