Genetic Variant NM_004925.5:c.390C>T (chr9-33442954-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_004925.5(AQP3):c.390C>T(p.Phe130Phe) 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

Publications

34 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
AQP3	NM_004925.5 link	c.390C>T	p.Phe130Phe	synonymous_variant	Exon 4 of 6	ENST00000297991.6	NP_004916.1	Q92482-1
AQP3	NM_001318144.2 link	c.390C>T	p.Phe130Phe	synonymous_variant	Exon 4 of 5		NP_001305073.1	Q92482A0A2R8Y2R4
AQP3	XM_047423348.1 link	c.*43C>T		3_prime_UTR_variant	Exon 4 of 4		XP_047279304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP3	ENST00000297991.6 link	c.390C>T	p.Phe130Phe	synonymous_variant	Exon 4 of 6	1	NM_004925.5	ENSP00000297991.4		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

GnomAD2 exomes

AF:

0.630

AC:

158488

AN:

251426

AF XY:

0.622

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 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

African (AFR)

AF:

0.744

AC:

24899

AN:

33470

American (AMR)

AF:

0.699

AC:

31259

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.544

AC:

14204

AN:

26134

East Asian (EAS)

AF:

0.702

AC:

27884

AN:

39694

South Asian (SAS)

AF:

0.584

AC:

50327

AN:

86236

European-Finnish (FIN)

AF:

0.680

AC:

36337

AN:

53412

Middle Eastern (MID)

AF:

0.546

AC:

3148

AN:

5764

European-Non Finnish (NFE)

AF:

0.591

AC:

657045

AN:

1111220

Other (OTH)

AF:

0.610

AC:

36852

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

20030

40060

60090

80120

100150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18122

36244

54366

72488

90610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.650

AC:

98838

AN:

152162

Hom.:

32654

Cov.:

AF XY:

0.653

AC XY:

48564

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.741

AC:

30768

AN:

41520

American (AMR)

AF:

0.674

AC:

10301

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.544

AC:

1890

AN:

3472

East Asian (EAS)

AF:

0.702

AC:

3631

AN:

5170

South Asian (SAS)

AF:

0.577

AC:

2779

AN:

4820

European-Finnish (FIN)

AF:

0.695

AC:

7361

AN:

10586

Middle Eastern (MID)

AF:

0.558

AC:

164

AN:

294

European-Non Finnish (NFE)

AF:

0.590

AC:

40127

AN:

67984

Other (OTH)

AF:

0.608

AC:

1283

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1819

3638

5456

7275

9094

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

794

1588

2382

3176

3970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.606

Hom.:

107339

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

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

-0.86

CADD

Benign

2.2

(source)

DANN

Benign

0.59

PhyloP100

0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over