dbSNP rs62542743: AQP7:p.Gly264Val (chr9-33385243-C-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

26 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AQP7	NM_001170.3 link	c.791G>T	p.Gly264Val	missense_variant	Exon 8 of 8	ENST00000297988.6	NP_001161.1	O14520-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP7	ENST00000297988.6 link	c.791G>T	p.Gly264Val	missense_variant	Exon 8 of 8	1	NM_001170.3	ENSP00000297988.1		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

GnomAD2 exomes

AF:

0.0380

AC:

9510

AN:

250394

AF XY:

0.0384

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 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

African (AFR)

AF:

0.00677

AC:

226

AN:

33406

American (AMR)

AF:

0.0267

AC:

1193

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0419

AC:

1094

AN:

26126

East Asian (EAS)

AF:

0.0223

AC:

886

AN:

39696

South Asian (SAS)

AF:

0.0266

AC:

2288

AN:

86158

European-Finnish (FIN)

AF:

0.0472

AC:

2516

AN:

53276

Middle Eastern (MID)

AF:

0.0271

AC:

112

AN:

4136

European-Non Finnish (NFE)

AF:

0.0527

AC:

58633

AN:

1111758

Other (OTH)

AF:

0.0425

AC:

2561

AN:

60204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

3815

7630

11444

15259

19074

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2220

4440

6660

8880

11100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0343

AC:

5217

AN:

152234

Hom.:

121

Cov.:

AF XY:

0.0347

AC XY:

2583

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.00893

AC:

371

AN:

41556

American (AMR)

AF:

0.0366

AC:

560

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0438

AC:

152

AN:

3468

East Asian (EAS)

AF:

0.0267

AC:

138

AN:

5170

South Asian (SAS)

AF:

0.0265

AC:

128

AN:

4822

European-Finnish (FIN)

AF:

0.0494

AC:

524

AN:

10608

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0476

AC:

3239

AN:

67992

Other (OTH)

AF:

0.0355

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

262

525

787

1050

1312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0383

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 QUANTITATIVE TRAIT LOCUS

Other:1

Jan 01, 2013

OMIM

Significance:Affects

Review Status:no assertion criteria provided

Collection Method:literature only

- -

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

(source)

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

PhyloP100

7.8

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

Mutation Taster

=77/23

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over