Variant 9-33385243-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP3BP4_StrongBA1

The NM_001170.3(AQP7):c.791G>T(p.Gly264Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0464 in 1,611,704 control chromosomes in the GnomAD database, including 1,902 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Affects (no stars).

Frequency

Genomes: 𝑓 0.034 ( 121 hom., cov: 32)

Exomes 𝑓: 0.048 ( 1781 hom. )

Consequence

AQP7
NM_001170.3 missense

Scores

Clinical Significance

Affects no assertion criteria provided O:1

Conservation

PhyloP100: 7.81

Variant links:

Genes affected

AQP7 (HGNC:640): (aquaporin 7) This gene encodes a member of the aquaporin family of water-selective membrane channels. The encoded protein localizes to the plasma membrane and allows movement of water, glycerol and urea across cell membranes. This gene is highly expressed in the adipose tissue where the encoded protein facilitates efflux of glycerol. In the proximal straight tubules of kidney, the encoded protein is localized to the apical membrane and prevents excretion of glycerol into urine. The encoded protein is present in spermatids, as well as in the testicular and epididymal spermatozoa suggesting an important role in late spermatogenesis. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. This gene is located adjacent to a related aquaporin gene on chromosome 9. Multiple pseudogenes of this gene have been identified. [provided by RefSeq, Dec 2015]

AQP7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 6: AlphaMissense, BayesDel_noAF, Cadd, Eigen, phyloP100way_vertebrate, PROVEAN [when BayesDel_addAF, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.008925259).

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AQP7	NM_001170.3 linkuse as main transcript	c.791G>T	p.Gly264Val	missense_variant	8/8	ENST00000297988.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AQP7	ENST00000297988.6 linkuse as main transcript	c.791G>T	p.Gly264Val	missense_variant	8/8	1	NM_001170.3	P2	O14520-1

Frequencies

GnomAD3 genomes

AF:

0.0343

AC:

5216

AN:

152116

Hom.:

121

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00895

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0366

Gnomad ASJ

AF:

0.0438

Gnomad EAS

AF:

0.0270

Gnomad SAS

AF:

0.0259

Gnomad FIN

AF:

0.0494

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0476

Gnomad OTH

AF:

0.0359

GnomAD3 exomes

AF:

0.0380

AC:

9510

AN:

250394

Hom.:

182

AF XY:

0.0384

AC XY:

5201

AN XY:

135436

show subpopulations

Gnomad AFR exome

AF:

0.00763

Gnomad AMR exome

AF:

0.0249

Gnomad ASJ exome

AF:

0.0402

Gnomad EAS exome

AF:

0.0311

Gnomad SAS exome

AF:

0.0250

Gnomad FIN exome

AF:

0.0457

Gnomad NFE exome

AF:

0.0489

Gnomad OTH exome

AF:

0.0444

GnomAD4 exome

AF:

0.0476

AC:

69509

AN:

1459470

Hom.:

1781

Cov.:

AF XY:

0.0471

AC XY:

34227

AN XY:

726050

show subpopulations

Gnomad4 AFR exome

AF:

0.00677

Gnomad4 AMR exome

AF:

0.0267

Gnomad4 ASJ exome

AF:

0.0419

Gnomad4 EAS exome

AF:

0.0223

Gnomad4 SAS exome

AF:

0.0266

Gnomad4 FIN exome

AF:

0.0472

Gnomad4 NFE exome

AF:

0.0527

Gnomad4 OTH exome

AF:

0.0425

GnomAD4 genome

AF:

0.0343

AC:

5217

AN:

152234

Hom.:

121

Cov.:

AF XY:

0.0347

AC XY:

2583

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00893

Gnomad4 AMR

AF:

0.0366

Gnomad4 ASJ

AF:

0.0438

Gnomad4 EAS

AF:

0.0267

Gnomad4 SAS

AF:

0.0265

Gnomad4 FIN

AF:

0.0494

Gnomad4 NFE

AF:

0.0476

Gnomad4 OTH

AF:

0.0355

Alfa

AF:

0.0374

Hom.:

Bravo

AF:

0.0336

TwinsUK

AF:

0.0531

AC:

197

ALSPAC

AF:

0.0488

AC:

188

ESP6500AA

AF:

0.0116

AC:

ESP6500EA

AF:

0.0488

AC:

420

ExAC

AF:

0.0365

AC:

4433

Asia WGS

AF:

0.0260

AC:

AN:

3478

EpiCase

AF:

0.0509

EpiControl

AF:

0.0492

ClinVar

Significance: Affects

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Glycerol release during exercise, defective

Other:1

Affects, no assertion criteria provided

literature only

OMIM

Jan 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Benign

0.0027

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.93

.;D

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

D;D

MetaRNN

Benign

0.0089

T;T

MetaSVM

Uncertain

-0.070

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-7.5

D;D

REVEL

Uncertain

0.58

Sift

Uncertain

0.0080

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.38

MPC

0.77

ClinPred

0.088

GERP RS

4.3

Varity_R

0.98

Splicing

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over