Variant 2-240682371-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001102467.2(AQP12B):c.467G>C(p.Arg156Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00085 ( 0 hom., cov: 23)

Exomes 𝑓: 0.00046 ( 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: -1.63

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07541394).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AQP12B	NM_001102467.2 linkuse as main transcript	c.467G>C	p.Arg156Pro	missense_variant	1/3	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.467G>C	p.Arg156Pro	missense_variant	1/3	1	NM_001102467.2	ENSP00000384894	P2	A6NM10-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

118

AN:

139532

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00101

Gnomad ASJ

AF:

0.00162

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000913

Gnomad FIN

AF:

0.000298

Gnomad MID

AF:

0.00373

Gnomad NFE

AF:

0.00132

Gnomad OTH

AF:

0.00163

GnomAD3 exomes

AF:

0.000304

AC:

AN:

131610

Hom.:

AF XY:

0.000283

AC XY:

AN XY:

70622

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000208

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000210

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000577

Gnomad OTH exome

AF:

0.000268

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000463

AC:

643

AN:

1388048

Hom.:

Cov.:

AF XY:

0.000465

AC XY:

318

AN XY:

683692

show subpopulations

Gnomad4 AFR exome

AF:

0.0000941

Gnomad4 AMR exome

AF:

0.000339

Gnomad4 ASJ exome

AF:

0.0000420

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000280

Gnomad4 FIN exome

AF:

0.000361

Gnomad4 NFE exome

AF:

0.000528

Gnomad4 OTH exome

AF:

0.000383

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000845

AC:

118

AN:

139630

Hom.:

Cov.:

AF XY:

0.000822

AC XY:

AN XY:

68118

show subpopulations

Gnomad4 AFR

AF:

0.000107

Gnomad4 AMR

AF:

0.00101

Gnomad4 ASJ

AF:

0.00162

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000914

Gnomad4 FIN

AF:

0.000298

Gnomad4 NFE

AF:

0.00132

Gnomad4 OTH

AF:

0.00161

Alfa

AF:

0.00147

Hom.:

ExAC

AF:

0.000134

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

Sep 20, 2023

The c.467G>C (p.R156P) alteration is located in exon 1 (coding exon 1) of the AQP12B gene. This alteration results from a G to C substitution at nucleotide position 467, causing the arginine (R) at amino acid position 156 to be replaced by a proline (P). 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

0.32

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Benign

-0.27

CADD

Benign

8.7

DANN

Benign

0.96

DEOGEN2

Uncertain

0.44

T;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.061

MetaRNN

Benign

0.075

T;T

MetaSVM

Benign

-0.44

MutationTaster

Benign

0.70

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-3.0

.;D

REVEL

Uncertain

0.36

Sift

Benign

0.17

.;T

Sift4G

Benign

0.087

T;T

Polyphen

0.66

.;P

Vest4

0.52

MVP

0.28

MPC

0.59

ClinPred

0.084

GERP RS

-1.3

Varity_R

0.17

gMVP

0.68

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