NM_004925.5:c.105G>C

Variant names:

• chr9-33447426-C-G
• rs591810
• NM_004925.5:c.105G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_004925.5(AQP3):​c.105G>C​(p.Leu35Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 1,596,606 control chromosomes in the GnomAD database, including 419,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.75 (43201 hom., cov: 32)
  • Exomes 𝑓: 0.72 (375932 hom.)
• Consequence: AQP3 NM_004925.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0520
• Publications: 24 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 9-33447426-C-G is Benign according to our data. Variant chr9-33447426-C-G is described in ClinVar as Benign. ClinVar VariationId is 3059468.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.052 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

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.105G>C	p.Leu35Leu	synonymous	Exon 1 of 6	NP_004916.1	Q92482-1
	AQP3	NM_001318144.2		c.105G>C	p.Leu35Leu	synonymous	Exon 1 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.105G>C	p.Leu35Leu	synonymous	Exon 1 of 6	ENSP00000297991.4	Q92482-1
	AQP3	ENST00000969970.1		c.105G>C	p.Leu35Leu	synonymous	Exon 1 of 5	ENSP00000640029.1
	AQP3	ENST00000645858.1		c.105G>C	p.Leu35Leu	synonymous	Exon 1 of 5	ENSP00000493516.1	A0A2R8Y2R4

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114144 AN: 152036 Hom.: 43153 Cov.: 32

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.722

GnomAD2 exomes AF: 0.728 AC: 158957 AN: 218270 AF XY: 0.720

Gnomad AFR exome AF: 0.776

Gnomad AMR exome AF: 0.812

Gnomad ASJ exome AF: 0.664

Gnomad EAS exome AF: 0.759

Gnomad FIN exome AF: 0.812

Gnomad NFE exome AF: 0.703

Gnomad OTH exome AF: 0.705

GnomAD4 exome AF: 0.720 AC: 1040437 AN: 1444452 Hom.: 375932 Cov.: 40 AF XY: 0.718 AC XY: 514550 AN XY: 716974

African (AFR) AF: 0.793 AC: 26326 AN: 33192

American (AMR) AF: 0.812 AC: 34432 AN: 42390

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 17170 AN: 25802

East Asian (EAS) AF: 0.721 AC: 28113 AN: 38992

South Asian (SAS) AF: 0.672 AC: 56208 AN: 83636

European-Finnish (FIN) AF: 0.816 AC: 42162 AN: 51664

Middle Eastern (MID) AF: 0.674 AC: 3869 AN: 5738

European-Non Finnish (NFE) AF: 0.715 AC: 789281 AN: 1103334

Other (OTH) AF: 0.718 AC: 42876 AN: 59704

GnomAD4 genome AF: 0.751 AC: 114247 AN: 152154 Hom.: 43201 Cov.: 32 AF XY: 0.754 AC XY: 56111 AN XY: 74396

African (AFR) AF: 0.790 AC: 32822 AN: 41522

American (AMR) AF: 0.798 AC: 12206 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2336 AN: 3470

East Asian (EAS) AF: 0.747 AC: 3856 AN: 5162

South Asian (SAS) AF: 0.657 AC: 3169 AN: 4826

European-Finnish (FIN) AF: 0.833 AC: 8845 AN: 10614

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.718 AC: 48776 AN: 67956

Other (OTH) AF: 0.716 AC: 1513 AN: 2112

Alfa AF: 0.699 Hom.: 9557

Bravo AF: 0.752

Asia WGS AF: 0.666 AC: 2316 AN: 3478

ClinVar

ClinVar submissions

Significance: 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
BayesDel_noAF	Benign	-0.39
CADD	Benign	8.1
DANN	Benign	0.80
PhyloP100		0.052
PromoterAI		0.049	Neutral
Mutation Taster		=97/3	polymorphism (auto)

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: rs591810; hg19: chr9-33447424; COSMIC: COSV107309430; COSMIC: COSV107309430;