9-33442300-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004925.5(AQP3):​c.710+1G>A variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.0000089 in 1,460,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Affects (no stars).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

AQP3
NM_004925.5 splice_donor, intron

Scores

4
2
1
Splicing: ADA: 1.000
2

Clinical Significance

Affects no assertion criteria provided O:1

Conservation

PhyloP100: 6.17
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AQP3NM_004925.5 linkc.710+1G>A splice_donor_variant, intron_variant Intron 5 of 5 ENST00000297991.6 NP_004916.1 Q92482-1
AQP3NM_001318144.2 linkc.493-89G>A intron_variant Intron 4 of 4 NP_001305073.1 Q92482A0A2R8Y2R4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AQP3ENST00000297991.6 linkc.710+1G>A splice_donor_variant, intron_variant Intron 5 of 5 1 NM_004925.5 ENSP00000297991.4 Q92482-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000890
AC:
13
AN:
1460340
Hom.:
0
Cov.:
33
AF XY:
0.00000551
AC XY:
4
AN XY:
726434
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000668
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Affects
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

GIL BLOOD GROUP Other:1
Affects, no assertion criteria providedliterature onlyOMIMNov 29, 2002- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.40
D
BayesDel_noAF
Pathogenic
0.34
CADD
Pathogenic
34
DANN
Uncertain
0.99
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
0.96
FATHMM_MKL
Uncertain
0.94
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.93
SpliceAI score (max)
0.93
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.59
Position offset: -3
DS_DL_spliceai
0.93
Position offset: 1

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.

Other links and lift over

dbSNP: rs1347380973; hg19: chr9-33442298; COSMIC: COSV99955714; COSMIC: COSV99955714; API