11-77590014-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173039.3(AQP11):c.22C>G(p.Arg8Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000444 in 1,507,530 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R8P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

AQP11
NM_173039.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.541

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.041315615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AQP11	NM_173039.3 linkuse as main transcript	c.22C>G	p.Arg8Gly	missense_variant	1/3	ENST00000313578.4
AQP11	NM_001363477.2 linkuse as main transcript	c.22C>G	p.Arg8Gly	missense_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
AQP11	ENST00000313578.4 linkuse as main transcript	c.22C>G	p.Arg8Gly	missense_variant	1/3	1	NM_173039.3	P1
AQP11	ENST00000528638.1 linkuse as main transcript	n.290+334C>G		intron_variant, non_coding_transcript_variant		1
CLNS1A	ENST00000526761.5 linkuse as main transcript	c.*156-4555G>C		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000188

AC:

AN:

159648

Hom.:

AF XY:

0.0000113

AC XY:

AN XY:

88760

show subpopulations

Gnomad AFR exome

AF:

0.0000861

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000255

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000450

AC:

AN:

1355426

Hom.:

Cov.:

AF XY:

0.0000375

AC XY:

AN XY:

666038

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:

0.00

Gnomad4 NFE exome

AF:

0.0000517

Gnomad4 OTH exome

AF:

0.000108

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000735

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 27, 2022

The c.22C>G (p.R8G) alteration is located in exon 1 (coding exon 1) of the AQP11 gene. This alteration results from a C to G substitution at nucleotide position 22, causing the arginine (R) at amino acid position 8 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.46

Cadd

Benign

0.95

Dann

Benign

0.68

DEOGEN2

Benign

0.095

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.60

M_CAP

Benign

0.0077

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

0.39

REVEL

Benign

0.019

Sift

Benign

0.14

Sift4G

Benign

0.14

Polyphen

0.0

Vest4

0.14

MVP

0.31

MPC

0.66

ClinPred

0.041

GERP RS

-1.7

Varity_R

0.077

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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