9-33385742-A-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001170.3(AQP7):c.650T>A(p.Leu217His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

AQP7
NM_001170.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.32

Publications

9 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0118846).

BP6

Variant 9-33385742-A-T is Benign according to our data. Variant chr9-33385742-A-T is described in ClinVar as Benign. ClinVar VariationId is 402385.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP7	NM_001170.3 link	c.650T>A	p.Leu217His	missense_variant	Exon 7 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.650T>A	p.Leu217His	missense_variant	Exon 7 of 8	1	NM_001170.3	ENSP00000297988.1		O14520-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00356

AC:

800

AN:

224876

AF XY:

0.00220

show subpopulations

Gnomad AFR exome

AF:

0.0228

Gnomad AMR exome

AF:

0.000118

Gnomad ASJ exome

AF:

0.00292

Gnomad EAS exome

AF:

0.000282

Gnomad FIN exome

AF:

0.00219

Gnomad NFE exome

AF:

0.00385

Gnomad OTH exome

AF:

0.00339

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461584

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727084

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5554

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1112004

Other (OTH)

AF:

0.00

AC:

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.137

Hom.:

ExAC

AF:

0.0518

AC:

6294

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Fails quality filter; no convincing gene-disease relationship -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

CADD

Benign

(source)

DANN

Benign

0.57

DEOGEN2

Uncertain

0.78

.;D;D;.;.;D;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.26

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.56

T;T;T;T;T;T;T

MetaRNN

Benign

0.012

T;T;T;T;T;T;T

MetaSVM

Benign

-0.38

PhyloP100

9.3

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.8

D;D;D;D;D;.;.

REVEL

Uncertain

0.47

Sift

Benign

0.085

T;T;T;T;T;.;.

Sift4G

Benign

0.075

T;D;T;.;T;T;T

Polyphen

0.0080, 0.0040, 0.014, 0.0060

.;B;B;.;B;B;.

Vest4

0.22

MPC

0.31

ClinPred

0.090

GERP RS

3.9

Varity_R

0.74

Mutation Taster

=48/52

disease causing

(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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over