chr11-77590605-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_173039.3(AQP11):c.613T>C(p.Tyr205His) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,611,254 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
AQP11
NM_173039.3 missense
NM_173039.3 missense
Scores
4
9
6
Clinical Significance
Conservation
PhyloP100: 5.07
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 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.24583802).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AQP11 | NM_173039.3 | c.613T>C | p.Tyr205His | missense_variant | 1/3 | ENST00000313578.4 | |
AQP11 | NM_001363477.2 | c.613T>C | p.Tyr205His | missense_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AQP11 | ENST00000313578.4 | c.613T>C | p.Tyr205His | missense_variant | 1/3 | 1 | NM_173039.3 | P1 | |
AQP11 | ENST00000528638.1 | n.367T>C | non_coding_transcript_exon_variant | 2/4 | 1 | ||||
CLNS1A | ENST00000526761.5 | c.*156-5146A>G | intron_variant, NMD_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152264Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000281 AC: 7AN: 249268Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134742
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1458990Hom.: 0 Cov.: 33 AF XY: 0.0000152 AC XY: 11AN XY: 725542
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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 | Nov 05, 2021 | The c.613T>C (p.Y205H) alteration is located in exon 1 (coding exon 1) of the AQP11 gene. This alteration results from a T to C substitution at nucleotide position 613, causing the tyrosine (Y) at amino acid position 205 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
B
Vest4
MVP
MPC
ClinPred
D
GERP RS
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