Variant 2-240682336-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 ENST00000407834.4(AQP12B):c.502G>A(p.Ala168Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000081 ( 0 hom., cov: 22)

Exomes 𝑓: 0.00010 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

AQP12B
ENST00000407834.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.526

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:

AQP12B (HGNC:):

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=0.047798604).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AQP12B	NM_001102467.2 linkuse as main transcript	c.502G>A	p.Ala168Thr	missense_variant	1/3	ENST00000407834.4	NP_001095937.1	A6NM10-2Q8IUS6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AQP12B	ENST00000407834.4 linkuse as main transcript	c.502G>A	p.Ala168Thr	missense_variant	1/3	1	NM_001102467.2	ENSP00000384894.3		A6NM10-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

148574

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000495

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000203

Gnomad SAS

AF:

0.000219

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000120

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000705

AC:

AN:

127638

Hom.:

AF XY:

0.0000729

AC XY:

AN XY:

68614

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000823

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000153

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000827

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000101

AC:

139

AN:

1369916

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

673622

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000801

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000178

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000111

Gnomad4 OTH exome

AF:

0.0000707

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000807

AC:

AN:

148686

Hom.:

Cov.:

AF XY:

0.0000966

AC XY:

AN XY:

72492

show subpopulations

Gnomad4 AFR

AF:

0.0000494

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000203

Gnomad4 SAS

AF:

0.000219

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000120

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000489

AC:

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

Mar 20, 2023

The c.502G>A (p.A168T) alteration is located in exon 1 (coding exon 1) of the AQP12B gene. This alteration results from a G to A substitution at nucleotide position 502, causing the alanine (A) at amino acid position 168 to be replaced by a threonine (T). 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

0.075

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

0.15

DANN

Benign

0.89

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.61

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.048

T;T

MetaSVM

Benign

-0.77

MutationTaster

Benign

1.0

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.74

.;N

REVEL

Benign

0.14

Sift

Benign

0.42

.;T

Sift4G

Benign

0.43

T;T

Polyphen

0.093

.;B

Vest4

0.14

MutPred

0.40

.;Loss of helix (P = 0.1706);

MVP

0.45

MPC

0.18

ClinPred

0.0082

GERP RS

-0.23

Varity_R

0.017

gMVP

0.28

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