chr9-33441997-A-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 8/9 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

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

Verdict is Benign. Variant got -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 id is 3052003.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 4 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP3	NM_004925.5	c.*46T>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000297991.6	NP_004916.1
AQP3	NM_001318144.2	c.707T>G	p.Ile236Ser	missense_variant	Exon 5 of 5		NP_001305073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP3	ENST00000297991	c.*46T>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_004925.5	ENSP00000297991.4
AQP3	ENST00000645858.1	c.707T>G	p.Ile236Ser	missense_variant	Exon 5 of 5			ENSP00000493516.1
AQP3	ENST00000493581.1	n.2070T>G		non_coding_transcript_exon_variant	Exon 2 of 2	2
AQP3	ENST00000494313.2	n.691T>G		non_coding_transcript_exon_variant	Exon 3 of 3	2

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

GnomAD3 exomes AF: 0.000950 AC: 231 AN: 243172 Hom.: 0 AF XY: 0.00107 AC XY: 140 AN XY: 131384

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 SAS exome AF: 0.00169

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

Gnomad4 AFR exome AF: 0.0000600

Gnomad4 AMR exome AF: 0.000113

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00206

Gnomad4 FIN exome AF: 0.00397

Gnomad4 NFE exome AF: 0.000514

Gnomad4 OTH exome AF: 0.000685

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

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00547

Gnomad4 NFE AF: 0.000676

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000666 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

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

AQP3-related disorder Benign:1

Jan 12, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs373432319; hg19: chr9-33441995;