NM_004925.5:c.253G>T

Variant names:

• chr9-33443441-C-A
• NM_004925.5:c.253G>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_004925.5(AQP3):​c.253G>T​(p.Ala85Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AQP3 NM_004925.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.15
• Publications: 0 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.948

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004925.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP3	NM_004925.5	MANE Select	c.253G>T	p.Ala85Ser	missense	Exon 3 of 6	NP_004916.1	Q92482-1
	AQP3	NM_001318144.2		c.253G>T	p.Ala85Ser	missense	Exon 3 of 5	NP_001305073.1	A0A2R8Y2R4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP3	ENST00000297991.6	TSL:1 MANE Select	c.253G>T	p.Ala85Ser	missense	Exon 3 of 6	ENSP00000297991.4	Q92482-1
	AQP3	ENST00000645858.1		c.253G>T	p.Ala85Ser	missense	Exon 3 of 5	ENSP00000493516.1	A0A2R8Y2R4
	AQP3	ENST00000969970.1		c.235+325G>T		intron	N/A	ENSP00000640029.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.94	D
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.069	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		6.2
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.018	D
Polyphen		0.96	D
Vest4		0.75
MutPred		0.92		Gain of glycosylation at A85 (P = 0.0525)
MVP		0.63
MPC		1.2
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.67
gMVP		0.88
Mutation Taster		=25/75	disease causing

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

Other links and lift over

hg19: chr9-33443439;