NM_004925.5:c.390C>G

Variant names:

• chr9-33442954-G-C
• rs2228332
• NM_004925.5:c.390C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004925.5(AQP3):​c.390C>G​(p.Phe130Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F130F) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AQP3 NM_004925.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158
• Publications: 34 publications found

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

Our verdict: Uncertain_significance. The variant received 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.390C>G	p.Phe130Leu	missense_variant	Exon 4 of 6	ENST00000297991.6	NP_004916.1
AQP3	NM_001318144.2	c.390C>G	p.Phe130Leu	missense_variant	Exon 4 of 5		NP_001305073.1
AQP3	XM_047423348.1	c.*43C>G		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	c.390C>G	p.Phe130Leu	missense_variant	Exon 4 of 6	1	NM_004925.5	ENSP00000297991.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.8
DANN	Benign	0.82
DEOGEN2	Pathogenic	0.87	D;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.
PhyloP100		0.16
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-4.7	D;.
REVEL	Benign	0.21
Sift	Benign	0.058	T;.
Sift4G	Benign	0.079	T;.
Polyphen		0.72	P;.
Vest4		0.59
MutPred		0.60		Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);
MVP		0.35
MPC		0.58
ClinPred		0.98	D
GERP RS		-6.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.57
gMVP		0.88
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

dbSNP: rs2228332; hg19: chr9-33442952;