Variant rs2228332 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_004925.5(AQP3):c.390C>T(p.Phe130=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 1,613,182 control chromosomes in the GnomAD database, including 300,625 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.65 ( 32654 hom., cov: 33)

Exomes 𝑓: 0.60 ( 267971 hom. )

Consequence

AQP3
NM_004925.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.158

Variant links:

Genes affected

AQP3 (HGNC:636): (aquaporin 3 (Gill blood group)) This gene encodes the water channel protein aquaporin 3. Aquaporins are a family of small integral membrane proteins related to the major intrinsic protein, also known as aquaporin 0. Aquaporin 3 is localized at the basal lateral membranes of collecting duct cells in the kidney. In addition to its water channel function, aquaporin 3 has been found to facilitate the transport of nonionic small solutes such as urea and glycerol, but to a smaller degree. It has been suggested that water channels can be functionally heterogeneous and possess water and solute permeation mechanisms. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

AQP3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 9-33442954-G-A is Benign according to our data. Variant chr9-33442954-G-A is described in ClinVar as [Benign]. Clinvar id is 3060388.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.158 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AQP3	NM_004925.5 linkuse as main transcript	c.390C>T	p.Phe130=	synonymous_variant	4/6	ENST00000297991.6
AQP3	NM_001318144.2 linkuse as main transcript	c.390C>T	p.Phe130=	synonymous_variant	4/5
AQP3	XM_047423348.1 linkuse as main transcript	c.*43C>T		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AQP3	ENST00000297991.6 linkuse as main transcript	c.390C>T	p.Phe130=	synonymous_variant	4/6	1	NM_004925.5	P1	Q92482-1

Frequencies

GnomAD3 genomes

AF:

0.650

AC:

98767

AN:

152044

Hom.:

32629

Cov.:

show subpopulations

Gnomad AFR

AF:

0.741

Gnomad AMI

AF:

0.586

Gnomad AMR

AF:

0.673

Gnomad ASJ

AF:

0.544

Gnomad EAS

AF:

0.702

Gnomad SAS

AF:

0.578

Gnomad FIN

AF:

0.695

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.590

Gnomad OTH

AF:

0.613

GnomAD3 exomes

AF:

0.630

AC:

158488

AN:

251426

Hom.:

50618

AF XY:

0.622

AC XY:

84523

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.748

Gnomad AMR exome

AF:

0.701

Gnomad ASJ exome

AF:

0.543

Gnomad EAS exome

AF:

0.718

Gnomad SAS exome

AF:

0.578

Gnomad FIN exome

AF:

0.684

Gnomad NFE exome

AF:

0.591

Gnomad OTH exome

AF:

0.602

GnomAD4 exome

AF:

0.604

AC:

881955

AN:

1461020

Hom.:

267971

Cov.:

AF XY:

0.602

AC XY:

437241

AN XY:

726870

show subpopulations

Gnomad4 AFR exome

AF:

0.744

Gnomad4 AMR exome

AF:

0.699

Gnomad4 ASJ exome

AF:

0.544

Gnomad4 EAS exome

AF:

0.702

Gnomad4 SAS exome

AF:

0.584

Gnomad4 FIN exome

AF:

0.680

Gnomad4 NFE exome

AF:

0.591

Gnomad4 OTH exome

AF:

0.610

GnomAD4 genome

AF:

0.650

AC:

98838

AN:

152162

Hom.:

32654

Cov.:

AF XY:

0.653

AC XY:

48564

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.741

Gnomad4 AMR

AF:

0.674

Gnomad4 ASJ

AF:

0.544

Gnomad4 EAS

AF:

0.702

Gnomad4 SAS

AF:

0.577

Gnomad4 FIN

AF:

0.695

Gnomad4 NFE

AF:

0.590

Gnomad4 OTH

AF:

0.608

Alfa

AF:

0.596

Hom.:

48257

Bravo

AF:

0.656

Asia WGS

AF:

0.601

AC:

2092

AN:

3478

EpiCase

AF:

0.588

EpiControl

AF:

0.588

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

AQP3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.2

DANN

Benign

0.59

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.

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