rs111572783

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001169.3(AQP8):​c.182C>A​(p.Thr61Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T61M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

AQP8
NM_001169.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.12
Variant links:
Genes affected
AQP8 (HGNC:642): (aquaporin 8) Aquaporin 8 (AQP8) is a water channel protein. Aquaporins are a family of small integral membrane proteins related to the major intrinsic protein (MIP or AQP0). Aquaporin 8 mRNA is found in pancreas and colon but not other tissues. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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=0.076096475).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AQP8NM_001169.3 linkc.182C>A p.Thr61Lys missense_variant Exon 2 of 6 ENST00000219660.6 NP_001160.2 O94778
AQP8XM_011545822.3 linkc.185C>A p.Thr62Lys missense_variant Exon 2 of 6 XP_011544124.1
AQP8XM_011545823.3 linkc.185C>A p.Thr62Lys missense_variant Exon 2 of 4 XP_011544125.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AQP8ENST00000219660.6 linkc.182C>A p.Thr61Lys missense_variant Exon 2 of 6 1 NM_001169.3 ENSP00000219660.5 O94778
AQP8ENST00000566125.5 linkc.164C>A p.Thr55Lys missense_variant Exon 2 of 6 1 ENSP00000454457.1 A0A0C4DGL6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461832
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
0.27
DANN
Benign
0.23
DEOGEN2
Benign
0.23
.;T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.080
N
LIST_S2
Benign
0.14
T;T
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.076
T;T
MetaSVM
Benign
-0.75
T
MutationAssessor
Benign
0.13
.;N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.37
N;N
REVEL
Benign
0.12
Sift
Benign
0.92
T;T
Sift4G
Benign
0.91
T;T
Polyphen
0.022
.;B
Vest4
0.22
MutPred
0.44
.;Gain of solvent accessibility (P = 0.0044);
MVP
0.61
MPC
0.27
ClinPred
0.035
T
GERP RS
-3.2
Varity_R
0.027
gMVP
0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-25228688; API