Genetic Variant AQP3:p.Leu35Leu (chr9-33447426-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_004925.5(AQP3):c.105G>C(p.Leu35Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 1,596,606 control chromosomes in the GnomAD database, including 419,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.75 ( 43201 hom., cov: 32)

Exomes 𝑓: 0.72 ( 375932 hom. )

Consequence

AQP3
NM_004925.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0520

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 9-33447426-C-G is Benign according to our data. Variant chr9-33447426-C-G is described in ClinVar as [Benign]. Clinvar id is 3059468.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.052 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP3	NM_004925.5 link	c.105G>C	p.Leu35Leu	synonymous_variant	Exon 1 of 6	ENST00000297991.6	NP_004916.1	Q92482-1
AQP3	NM_001318144.2 link	c.105G>C	p.Leu35Leu	synonymous_variant	Exon 1 of 5		NP_001305073.1	Q92482A0A2R8Y2R4
AQP3	XM_047423348.1 link	c.105G>C	p.Leu35Leu	synonymous_variant	Exon 1 of 4		XP_047279304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP3	ENST00000297991.6 link	c.105G>C	p.Leu35Leu	synonymous_variant	Exon 1 of 6	1	NM_004925.5	ENSP00000297991.4		Q92482-1

Frequencies

GnomAD3 genomes

AF:

0.751

AC:

114144

AN:

152036

Hom.:

43153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.790

Gnomad AMI

AF:

0.587

Gnomad AMR

AF:

0.798

Gnomad ASJ

AF:

0.673

Gnomad EAS

AF:

0.747

Gnomad SAS

AF:

0.657

Gnomad FIN

AF:

0.833

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.718

Gnomad OTH

AF:

0.722

GnomAD3 exomes

AF:

0.728

AC:

158957

AN:

218270

Hom.:

58275

AF XY:

0.720

AC XY:

85148

AN XY:

118264

show subpopulations

Gnomad AFR exome

AF:

0.776

Gnomad AMR exome

AF:

0.812

Gnomad ASJ exome

AF:

0.664

Gnomad EAS exome

AF:

0.759

Gnomad SAS exome

AF:

0.650

Gnomad FIN exome

AF:

0.812

Gnomad NFE exome

AF:

0.703

Gnomad OTH exome

AF:

0.705

GnomAD4 exome

AF:

0.720

AC:

1040437

AN:

1444452

Hom.:

375932

Cov.:

AF XY:

0.718

AC XY:

514550

AN XY:

716974

show subpopulations

Gnomad4 AFR exome

AF:

0.793

Gnomad4 AMR exome

AF:

0.812

Gnomad4 ASJ exome

AF:

0.665

Gnomad4 EAS exome

AF:

0.721

Gnomad4 SAS exome

AF:

0.672

Gnomad4 FIN exome

AF:

0.816

Gnomad4 NFE exome

AF:

0.715

Gnomad4 OTH exome

AF:

0.718

GnomAD4 genome

AF:

0.751

AC:

114247

AN:

152154

Hom.:

43201

Cov.:

AF XY:

0.754

AC XY:

56111

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.790

Gnomad4 AMR

AF:

0.798

Gnomad4 ASJ

AF:

0.673

Gnomad4 EAS

AF:

0.747

Gnomad4 SAS

AF:

0.657

Gnomad4 FIN

AF:

0.833

Gnomad4 NFE

AF:

0.718

Gnomad4 OTH

AF:

0.716

Alfa

AF:

0.699

Hom.:

9557

Bravo

AF:

0.752

Asia WGS

AF:

0.666

AC:

2316

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

AQP3-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

-0.39

CADD

Benign

8.1

DANN

Benign

0.80

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