11-77609341-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_173039.3(AQP11):c.780G>T(p.Trp260Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000322 in 1,612,410 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
AQP11
NM_173039.3 missense
NM_173039.3 missense
Scores
11
8
Clinical Significance
Conservation
PhyloP100: 4.72
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]
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AQP11 | NM_173039.3 | c.780G>T | p.Trp260Cys | missense_variant | 3/3 | ENST00000313578.4 | |
AQP11 | NM_001363477.2 | c.663G>T | p.Trp221Cys | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AQP11 | ENST00000313578.4 | c.780G>T | p.Trp260Cys | missense_variant | 3/3 | 1 | NM_173039.3 | P1 | |
AQP11 | ENST00000528638.1 | n.534G>T | non_coding_transcript_exon_variant | 4/4 | 1 | ||||
CLNS1A | ENST00000526761.5 | c.*155+1974C>A | intron_variant, NMD_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000198 AC: 3AN: 151752Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000279 AC: 7AN: 250592Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135454
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GnomAD4 exome AF: 0.0000335 AC: 49AN: 1460658Hom.: 0 Cov.: 30 AF XY: 0.0000385 AC XY: 28AN XY: 726650
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Nov 26, 2018 | The AQP11 c.780G>T (p.Trp260Cys) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found through this search. This variant is reported a frequency of 0.000063 in the European (Non-Finnish) population of the Genome Aggregation Database. Based on the available evidence, the p.Trp260Cys variant is classified as a variant of uncertain significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
T
Polyphen
D
Vest4
MutPred
Loss of catalytic residue at L258 (P = 0.0215);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at