11-77590427-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_173039.3(AQP11):c.435G>T(p.Gln145His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00576 in 1,614,088 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q145P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0043 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0059 ( 37 hom. )

Consequence

AQP11
NM_173039.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.305

Variant links:

Genes affected

AQP11 (HGNC:19940): (aquaporin 11) Enables glycerol channel activity and water channel activity. Involved in several processes, including glycerol transport; hydrogen peroxide transmembrane transport; and protein homooligomerization. Located in cell surface; endoplasmic reticulum; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

AQP11 links:

CLNS1A (HGNC:2080): (chloride nucleotide-sensitive channel 1A) This gene encodes a protein that functions in multiple regulatory pathways. The encoded protein complexes with numerous cytosolic proteins and performs diverse functions including regulation of small nuclear ribonucleoprotein biosynthesis, platelet activation and cytoskeletal organization. The protein is also found associated with the plasma membrane where it functions as a chloride current regulator. Pseudogenes of this gene are found on chromosomes 1, 4 and 6. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2015]

CLNS1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0056094825).

BP6

Variant 11-77590427-G-T is Benign according to our data. Variant chr11-77590427-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642191.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP11	NM_173039.3 link	c.435G>T	p.Gln145His	missense_variant	Exon 1 of 3	ENST00000313578.4	NP_766627.1	Q8NBQ7
AQP11	NM_001363477.2 link	c.435G>T	p.Gln145His	missense_variant	Exon 1 of 2		NP_001350406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AQP11	ENST00000313578.4 link	c.435G>T	p.Gln145His	missense_variant	Exon 1 of 3	1	NM_173039.3	ENSP00000318770.3	Q8NBQ7
AQP11	ENST00000528638.1 link	n.291-102G>T		intron_variant	Intron 1 of 3	1
CLNS1A	ENST00000526761.5 link	n.*156-4968C>A		intron_variant	Intron 3 of 5	3		ENSP00000475218.1	U3KPU0

Frequencies

GnomAD3 genomes

AF:

0.00433

AC:

659

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00890

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00622

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00395

AC:

993

AN:

251434

Hom.:

AF XY:

0.00406

AC XY:

552

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00494

Gnomad ASJ exome

AF:

0.00218

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00144

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.00613

Gnomad OTH exome

AF:

0.00538

GnomAD4 exome

AF:

0.00591

AC:

8641

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00582

AC XY:

4229

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00119

Gnomad4 AMR exome

AF:

0.00530

Gnomad4 ASJ exome

AF:

0.00253

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00134

Gnomad4 FIN exome

AF:

0.000337

Gnomad4 NFE exome

AF:

0.00696

Gnomad4 OTH exome

AF:

0.00621

GnomAD4 genome

AF:

0.00432

AC:

658

AN:

152248

Hom.:

Cov.:

AF XY:

0.00414

AC XY:

308

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00173

Gnomad4 AMR

AF:

0.00889

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00622

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00613

Hom.:

Bravo

AF:

0.00461

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.00205

AC:

ESP6500EA

AF:

0.00524

AC:

ExAC

AF:

0.00368

AC:

447

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00883

EpiControl

AF:

0.00688

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

AQP11: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.38

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.45

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.0056

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.2

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.4

REVEL

Benign

0.093

Sift

Benign

0.067

Sift4G

Uncertain

0.042

Polyphen

0.0

Vest4

0.021

MutPred

0.38

Gain of catalytic residue at Q145 (P = 0.06);

MVP

0.79

MPC

0.83

ClinPred

0.0059

GERP RS

2.5

Varity_R

0.064

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over