NM_004925.5:c.132C>T

Variant names:

• chr9-33443869-G-A
• rs2228333
• NM_004925.5:c.132C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_004925.5(AQP3):​c.132C>T​(p.Ala44Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00593 in 1,613,894 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (48 hom.)
• Consequence: AQP3 NM_004925.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.146
• Publications: 2 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 9-33443869-G-A is Benign according to our data. Variant chr9-33443869-G-A is described in ClinVar as Benign. ClinVar VariationId is 719911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.146 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 6 BG gene

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.132C>T	p.Ala44Ala	synonymous	Exon 2 of 6	NP_004916.1	Q92482-1
	AQP3	NM_001318144.2		c.132C>T	p.Ala44Ala	synonymous	Exon 2 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.132C>T	p.Ala44Ala	synonymous	Exon 2 of 6	ENSP00000297991.4	Q92482-1
	AQP3	ENST00000969970.1		c.132C>T	p.Ala44Ala	synonymous	Exon 2 of 5	ENSP00000640029.1
	AQP3	ENST00000645858.1		c.132C>T	p.Ala44Ala	synonymous	Exon 2 of 5	ENSP00000493516.1	A0A2R8Y2R4

Frequencies

GnomAD3 genomes AF: 0.00465 AC: 707 AN: 152154 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.000893

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0131

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00753

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00519 AC: 1301 AN: 250746 AF XY: 0.00510

Gnomad AFR exome AF: 0.00124

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0120

Gnomad NFE exome AF: 0.00855

Gnomad OTH exome AF: 0.00425

GnomAD4 exome AF: 0.00606 AC: 8863 AN: 1461622 Hom.: 48 Cov.: 32 AF XY: 0.00582 AC XY: 4234 AN XY: 727106

African (AFR) AF: 0.000747 AC: 25 AN: 33472

American (AMR) AF: 0.000358 AC: 16 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00180 AC: 47 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86212

European-Finnish (FIN) AF: 0.0129 AC: 690 AN: 53376

Middle Eastern (MID) AF: 0.000874 AC: 5 AN: 5718

European-Non Finnish (NFE) AF: 0.00698 AC: 7764 AN: 1111916

Other (OTH) AF: 0.00522 AC: 315 AN: 60388

GnomAD4 genome AF: 0.00464 AC: 707 AN: 152272 Hom.: 6 Cov.: 32 AF XY: 0.00453 AC XY: 337 AN XY: 74450

African (AFR) AF: 0.000891 AC: 37 AN: 41542

American (AMR) AF: 0.000588 AC: 9 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.0131 AC: 139 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00753 AC: 512 AN: 68022

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00523 Hom.: 1

Bravo AF: 0.00350

EpiCase AF: 0.00627

EpiControl AF: 0.00646

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.5
DANN	Benign	0.78
PhyloP100		-0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=96/4	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: rs2228333; hg19: chr9-33443867;