Variant 2-240680386-C-A 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.690G>T(p.Glu230Asp) 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 0.00042 ( 0 hom., cov: 14)

Exomes 𝑓: 0.00061 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

AQP12B
NM_001102467.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.188

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=0.063812435).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AQP12B	NM_001102467.2 linkuse as main transcript	c.690G>T	p.Glu230Asp	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.690G>T	p.Glu230Asp	missense_variant	2/3	1	NM_001102467.2	ENSP00000384894	P2	A6NM10-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

115204

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000124

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000345

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:

0.000760

Gnomad OTH

AF:

0.000709

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000606

AC:

391

AN:

645148

Hom.:

Cov.:

AF XY:

0.000613

AC XY:

207

AN XY:

337448

show subpopulations

Gnomad4 AFR exome

AF:

0.000109

Gnomad4 AMR exome

AF:

0.000464

Gnomad4 ASJ exome

AF:

0.0000557

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000221

Gnomad4 NFE exome

AF:

0.000878

Gnomad4 OTH exome

AF:

0.000460

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000425

AC:

AN:

115342

Hom.:

Cov.:

AF XY:

0.000401

AC XY:

AN XY:

54908

show subpopulations

Gnomad4 AFR

AF:

0.000123

Gnomad4 AMR

AF:

0.000345

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000760

Gnomad4 OTH

AF:

0.000703

Alfa

AF:

0.000556

Hom.:

ExAC

AF:

0.000194

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

Jun 24, 2022

The c.690G>T (p.E230D) alteration is located in exon 2 (coding exon 2) of the AQP12B gene. This alteration results from a G to T substitution at nucleotide position 690, causing the glutamic acid (E) at amino acid position 230 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

Benign

0.24

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.21

T;.

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.044

MetaRNN

Benign

0.064

T;T

MetaSVM

Benign

-0.55

MutationTaster

Benign

0.55

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.7

.;N

REVEL

Benign

0.24

Sift

Benign

0.12

.;T

Sift4G

Benign

0.20

T;T

Polyphen

0.28

.;B

Vest4

0.15

MutPred

0.56

.;Loss of sheet (P = 0.1398);

MVP

0.41

MPC

0.25

ClinPred

0.10

GERP RS

2.2

Varity_R

0.058

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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