11-77590254-G-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_173039.3(AQP11):c.262G>T(p.Val88Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,601,184 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

AQP11
NM_173039.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.67

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3812795).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP11	NM_173039.3 link	c.262G>T	p.Val88Leu	missense_variant	Exon 1 of 3	ENST00000313578.4	NP_766627.1	Q8NBQ7
AQP11	NM_001363477.2 link	c.262G>T	p.Val88Leu	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.262G>T	p.Val88Leu	missense_variant	Exon 1 of 3	1	NM_173039.3	ENSP00000318770.3	Q8NBQ7
AQP11	ENST00000528638.1 link	n.291-275G>T		intron_variant	Intron 1 of 3	1
CLNS1A	ENST00000526761.5 link	n.*156-4795C>A		intron_variant	Intron 3 of 5	3		ENSP00000475218.1	U3KPU0

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152224

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:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000577

AC:

AN:

242540

Hom.:

AF XY:

0.0000535

AC XY:

AN XY:

130774

show subpopulations

Gnomad AFR exome

AF:

0.0000619

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:

0.0000477

Gnomad NFE exome

AF:

0.000100

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.000117

AC:

170

AN:

1448960

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

719242

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

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:

0.0000765

Gnomad4 NFE exome

AF:

0.000149

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74366

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:

0.000188

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000127

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 31, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.262G>T (p.V88L) alteration is located in exon 1 (coding exon 1) of the AQP11 gene. This alteration results from a G to T substitution at nucleotide position 262, causing the valine (V) at amino acid position 88 to be replaced by a leucine (L). 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

0.21

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.68

M_CAP

Benign

0.0088

MetaRNN

Benign

0.38

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.3

REVEL

Benign

0.061

Sift

Benign

0.36

Sift4G

Benign

0.57

Polyphen

0.77

Vest4

0.075

MutPred

0.65

Loss of helix (P = 0.2662);

MVP

0.73

MPC

1.4

ClinPred

0.17

GERP RS

4.6

Varity_R

0.13

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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