9-33441997-A-T

Variant names:

• chr9-33441997-A-T
• rs373432319
• NM_004925.5:c.*46T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001318144.2(AQP3):​c.707T>A​(p.Ile236Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/11 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I236S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AQP3 NM_001318144.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13231423).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318144.2. 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.*46T>A		3_prime_UTR	Exon 6 of 6	NP_004916.1	Q92482-1
	AQP3	NM_001318144.2		c.707T>A	p.Ile236Asn	missense	Exon 5 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.*46T>A		3_prime_UTR	Exon 6 of 6	ENSP00000297991.4	Q92482-1
	AQP3	ENST00000645858.1		c.707T>A	p.Ile236Asn	missense	Exon 5 of 5	ENSP00000493516.1	A0A2R8Y2R4
	AQP3	ENST00000969970.1		c.*46T>A		3_prime_UTR	Exon 5 of 5	ENSP00000640029.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.7
DANN	Benign	0.85
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.13	T
PhyloP100		-0.17
GERP RS		1.4
Mutation Taster		=100/0	polymorphism

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

dbSNP: rs373432319; hg19: chr9-33441995;