rs373432319

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr9-33441997-A-C
• chr9-33441997-A-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001318144.2(AQP3):​c.707T>G​(p.Ile236Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000704 in 1,602,054 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00076 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00070 (4 hom.)
• Consequence: AQP3 NM_001318144.2 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0057239234).
• BP6: Variant 9-33441997-A-C is Benign according to our data. Variant chr9-33441997-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3052003.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 4 BG gene

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>G		3_prime_UTR	Exon 6 of 6	NP_004916.1	Q92482-1
	AQP3	NM_001318144.2		c.707T>G	p.Ile236Ser	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>G		3_prime_UTR	Exon 6 of 6	ENSP00000297991.4	Q92482-1
	AQP3	ENST00000645858.1		c.707T>G	p.Ile236Ser	missense	Exon 5 of 5	ENSP00000493516.1	A0A2R8Y2R4
	AQP3	ENST00000969970.1		c.*46T>G		3_prime_UTR	Exon 5 of 5	ENSP00000640029.1

Frequencies

GnomAD3 genomes AF: 0.000762 AC: 116 AN: 152134 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00547

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000676

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000950 AC: 231 AN: 243172 AF XY: 0.00107

Gnomad AFR exome AF: 0.0000626

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00443

Gnomad NFE exome AF: 0.000702

Gnomad OTH exome AF: 0.00118

GnomAD4 exome AF: 0.000698 AC: 1012 AN: 1449802 Hom.: 4 Cov.: 32 AF XY: 0.000728 AC XY: 524 AN XY: 719654

African (AFR) AF: 0.0000600 AC: 2 AN: 33332

American (AMR) AF: 0.000113 AC: 5 AN: 44252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25428

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39522

South Asian (SAS) AF: 0.00206 AC: 175 AN: 84822

European-Finnish (FIN) AF: 0.00397 AC: 207 AN: 52094

Middle Eastern (MID) AF: 0.00228 AC: 13 AN: 5714

European-Non Finnish (NFE) AF: 0.000514 AC: 568 AN: 1104768

Other (OTH) AF: 0.000685 AC: 41 AN: 59870

GnomAD4 genome AF: 0.000762 AC: 116 AN: 152252 Hom.: 1 Cov.: 33 AF XY: 0.00103 AC XY: 77 AN XY: 74418

African (AFR) AF: 0.0000241 AC: 1 AN: 41542

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4824

European-Finnish (FIN) AF: 0.00547 AC: 58 AN: 10612

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

European-Non Finnish (NFE) AF: 0.000676 AC: 46 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000486 Hom.: 0

Bravo AF: 0.000298

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00107 AC: 130

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	AQP3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.7
DANN	Benign	0.77
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.22	T
MetaRNN	Benign	0.0057	T
PhyloP100		-0.17
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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;