Variant rs201263790 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_020980.5(AQP9):c.587T>A(p.Ile196Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

AQP9
NM_020980.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.27

Variant links:

Genes affected

AQP9 (HGNC:643): (aquaporin 9) The aquaporins are a family of water-selective membrane channels. This gene encodes a member of a subset of aquaporins called the aquaglyceroporins. This protein allows passage of a broad range of noncharged solutes and also stimulates urea transport and osmotic water permeability. This protein may also facilitate the uptake of glycerol in hepatic tissue . The encoded protein may also play a role in specialized leukocyte functions such as immunological response and bactericidal activity. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

AQP9 links:

ALDH1A2 (HGNC:15472): (aldehyde dehydrogenase 1 family member A2) This protein belongs to the aldehyde dehydrogenase family of proteins. The product of this gene is an enzyme that catalyzes the synthesis of retinoic acid (RA) from retinaldehyde. Retinoic acid, the active derivative of vitamin A (retinol), is a hormonal signaling molecule that functions in developing and adult tissues. The studies of a similar mouse gene suggest that this enzyme and the cytochrome CYP26A1, concurrently establish local embryonic retinoic acid levels which facilitate posterior organ development and prevent spina bifida. Four transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, May 2011]

ALDH1A2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.955

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP9	NM_020980.5 link	c.587T>A	p.Ile196Asn	missense_variant	Exon 5 of 6	ENST00000219919.9	NP_066190.2	O43315
AQP9	NM_001320636.1 link	c.392T>A	p.Ile131Asn	missense_variant	Exon 5 of 6		NP_001307565.1	H0YK62
AQP9	NM_001320635.2 link	c.495+4183T>A		intron_variant	Intron 4 of 4		NP_001307564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP9	ENST00000219919.9 link	c.587T>A	p.Ile196Asn	missense_variant	Exon 5 of 6	1	NM_020980.5	ENSP00000219919.4		O43315

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251206

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135752

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.81

D;D;D

Eigen

Pathogenic

0.74

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.96

D;.;D

M_CAP

Uncertain

0.26

MetaRNN

Pathogenic

0.96

D;D;D

MetaSVM

Uncertain

0.61

MutationAssessor

Pathogenic

3.6

.;H;H

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-5.9

D;D;D

REVEL

Uncertain

0.56

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

0.98

.;D;D

Vest4

0.77

MutPred

0.74

.;Loss of stability (P = 0.0255);Loss of stability (P = 0.0255);

MVP

0.97

MPC

0.061

ClinPred

1.0

GERP RS

5.9

Varity_R

0.80

gMVP

0.99

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over