9-33385692-G-T

Position:

chr9-33385692-G-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM2PP3BP4_StrongBP6_Moderate

The NM_001170.3(AQP7):c.700C>A(p.Arg234Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,613,622 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: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

AQP7
NM_001170.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.20

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:

AQP7 (HGNC:):

AQP7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Multiple lines of computational evidence support a deleterious effect 5: AlphaMissense, BayesDel_addAF, Cadd, FATHMM_MKL, PROVEAN [when MetaRNN, MutationTaster, phyloP100way_vertebrate was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.0114274025).

BP6

Variant 9-33385692-G-T is Benign according to our data. Variant chr9-33385692-G-T is described in ClinVar as [Benign]. Clinvar id is 402384.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AQP7	NM_001170.3 linkuse as main transcript	c.700C>A	p.Arg234Ser	missense_variant	7/8	ENST00000297988.6	NP_001161.1	O14520-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AQP7	ENST00000297988.6 linkuse as main transcript	c.700C>A	p.Arg234Ser	missense_variant	7/8	1	NM_001170.3	ENSP00000297988.1		O14520-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00369

AC:

787

AN:

213564

Hom.:

AF XY:

0.00276

AC XY:

325

AN XY:

117860

show subpopulations

Gnomad AFR exome

AF:

0.00392

Gnomad AMR exome

AF:

0.000753

Gnomad ASJ exome

AF:

0.00197

Gnomad EAS exome

AF:

0.00118

Gnomad SAS exome

AF:

0.000571

Gnomad FIN exome

AF:

0.0205

Gnomad NFE exome

AF:

0.00410

Gnomad OTH exome

AF:

0.00202

GnomAD4 exome

AF:

0.0000274

AC:

AN:

1461544

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0775

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0522

AC:

6338

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.63

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

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.79

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

MetaRNN

Benign

0.011

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

MetaSVM

Benign

-0.64

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-5.0

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

REVEL

Uncertain

0.37

Sift

Uncertain

0.025

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

Sift4G

Uncertain

0.027

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

Polyphen

0.53, 0.80, 0.97, 0.87

.;P;P;.;D;P;.

Vest4

0.35

MPC

0.38

ClinPred

0.038

GERP RS

4.1

Varity_R

0.92

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