chr9-33447497-C-A

Variant names:

• chr9-33447497-C-A
• rs773909054
• NM_004925.5:c.34G>T

Variant summary

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

The NM_004925.5(AQP3):​c.34G>T​(p.Gly12Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,188 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: AQP3 NM_004925.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.85

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]

ACMG classification

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
AQP3	NM_004925.5	c.34G>T	p.Gly12Trp	missense_variant	Exon 1 of 6	ENST00000297991.6	NP_004916.1
AQP3	NM_001318144.2	c.34G>T	p.Gly12Trp	missense_variant	Exon 1 of 5		NP_001305073.1
AQP3	XM_047423348.1	c.34G>T	p.Gly12Trp	missense_variant	Exon 1 of 4		XP_047279304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP3	ENST00000297991.6	c.34G>T	p.Gly12Trp	missense_variant	Exon 1 of 6	1	NM_004925.5	ENSP00000297991.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000425 AC: 1 AN: 235310 Hom.: 0 AF XY: 0.00000782 AC XY: 1 AN XY: 127950

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000342

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457188 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 724426

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: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000248 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.72	T;T
M_CAP	Pathogenic	0.69	D
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Uncertain	0.45	D
MutationAssessor	Benign	1.8	L;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.70	N;.
REVEL	Uncertain	0.42
Sift	Uncertain	0.0050	D;.
Sift4G	Uncertain	0.016	D;.
Polyphen		0.98	D;.
Vest4		0.53
MutPred		0.50		Gain of helix (P = 0.0128);Gain of helix (P = 0.0128);
MVP		0.71
MPC		1.1
ClinPred		0.98	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.22
gMVP		0.65

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

Other links and lift over

dbSNP: rs773909054; hg19: chr9-33447495; COSMIC: COSV99955641; COSMIC: COSV99955641;