17-81955512-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_178493.6(NOTUM):c.1021G>A(p.Glu341Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,611,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
NOTUM
NM_178493.6 missense
NM_178493.6 missense
Scores
5
9
5
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.39
Genes affected
NOTUM (HGNC:27106): (notum, palmitoleoyl-protein carboxylesterase) Enables palmitoleyl hydrolase activity. Involved in negative regulation of Wnt signaling pathway and protein depalmitoleylation. Acts upstream of or within bone development and regulation of bone mineralization. Predicted to be located in endoplasmic reticulum lumen and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.836
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTUM | NM_178493.6 | c.1021G>A | p.Glu341Lys | missense_variant | 9/11 | ENST00000409678.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTUM | ENST00000409678.8 | c.1021G>A | p.Glu341Lys | missense_variant | 9/11 | 1 | NM_178493.6 | P1 | |
ENST00000415556.2 | n.1828C>T | non_coding_transcript_exon_variant | 3/3 | 4 | |||||
NOTUM | ENST00000477214.5 | downstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152014Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000827 AC: 2AN: 241806Hom.: 0 AF XY: 0.00000753 AC XY: 1AN XY: 132768
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1459316Hom.: 0 Cov.: 32 AF XY: 0.00000964 AC XY: 7AN XY: 725964
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152130Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74388
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Benign
D
Sift4G
Uncertain
T
Polyphen
D
Vest4
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MPC
ClinPred
D
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