Variant chr9-33441997-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001318144.2(AQP3):c.707T>G(p.Ile236Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000704 in 1,602,054 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00076 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00070 ( 4 hom. )

Consequence

AQP3
NM_001318144.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.172

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0057239234).

BP6

Variant 9-33441997-A-C is Benign according to our data. Variant chr9-33441997-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3052003.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP3	NM_004925.5 link	c.*46T>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000297991.6	NP_004916.1	Q92482-1
AQP3	NM_001318144.2 link	c.707T>G	p.Ile236Ser	missense_variant	Exon 5 of 5		NP_001305073.1	Q92482A0A2R8Y2R4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AQP3	ENST00000297991 link	c.*46T>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_004925.5	ENSP00000297991.4	Q92482-1
AQP3	ENST00000645858.1 link	c.707T>G	p.Ile236Ser	missense_variant	Exon 5 of 5			ENSP00000493516.1	A0A2R8Y2R4
AQP3	ENST00000493581.1 link	n.2070T>G		non_coding_transcript_exon_variant	Exon 2 of 2	2
AQP3	ENST00000494313.2 link	n.691T>G		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.000762

AC:

116

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00547

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000950

AC:

231

AN:

243172

Hom.:

AF XY:

0.00107

AC XY:

140

AN XY:

131384

show subpopulations

Gnomad AFR exome

AF:

0.0000626

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00169

Gnomad FIN exome

AF:

0.00443

Gnomad NFE exome

AF:

0.000702

Gnomad OTH exome

AF:

0.00118

GnomAD4 exome

AF:

0.000698

AC:

1012

AN:

1449802

Hom.:

Cov.:

AF XY:

0.000728

AC XY:

524

AN XY:

719654

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00206

Gnomad4 FIN exome

AF:

0.00397

Gnomad4 NFE exome

AF:

0.000514

Gnomad4 OTH exome

AF:

0.000685

GnomAD4 genome

AF:

0.000762

AC:

116

AN:

152252

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00547

Gnomad4 NFE

AF:

0.000676

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000666

Hom.:

Bravo

AF:

0.000298

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00107

AC:

130

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

AQP3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 12, 2023

This variant is classified as likely 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

-0.74

CADD

Benign

9.7

DANN

Benign

0.77

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.22

MetaRNN

Benign

0.0057

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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