Yum, tasty mutations...

mutation t@sting

 documentation

Prediction

disease causing

 Model: simple_aae, prob: 0.999999849549449      (explain)
Summary
  • amino acid sequence changed
  • known as potential disease variant: rs18097 (probable pathogenic)
  • known disease mutation at this position (HGMD CM990168)
  • protein features (might be) affected
  • splice site changes
 hyperlink
analysed issue analysis result
name of alteration no title
alteration (phys. location) chr21:27264102C>TN/A show variant in all transcripts   IGV
HGNC symbol APP
Ensembl transcript ID ENST00000346798
Genbank transcript ID NM_000484
UniProt peptide P05067
alteration type single base exchange
alteration region CDS
DNA changes c.2143G>A
cDNA.2177G>A
g.279345G>A
AA changes V715M Score: 21 explain score(s)
position(s) of altered AA
if AA alteration in CDS		 715
frameshift no
known variant Reference ID: rs63750734
Allele 'T' was neither found in ExAC nor 1000G.
known as potential disease variant: rs18097 (probable pathogenic for Alzheimer disease, type 1|not provided) dbSNP  NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM990168)

known disease mutation at this position, please check HGMD for details (HGMD ID CM990168)
known disease mutation at this position, please check HGMD for details (HGMD ID CM990168)
regulatory features H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
phyloP / phastCons
PhyloPPhastCons
(flanking)4.7451
3.5871
(flanking)-0.570.866
explain score(s) and/or inspect your position(s) in in UCSC Genome Browser
splice sites
effectgDNA positionscorewt detection sequence exon-intron border
Donor marginally increased279338wt: 0.7499 / mu: 0.7569 (marginal change - not scored)wt: GTCATAGCGACAGTG
mu: GTCATAGCGACAATG		 CATA|gcga
Donor gained2793400.98mu: CATAGCGACAATGAT TAGC|gaca
distance from splice site 69
Kozak consensus sequence altered? N/A
conservation
protein level for non-synonymous changes
speciesmatchgeneaaalignment
Human      715GLMVGGVVIATVIVITLVMLKKKQ
mutated  all conserved    715GLMVGGVVIATMIVITL
Ptroglodytes  all identical  ENSPTRG00000013811  715GLMVGGVVIATVIVITL
Mmulatta  all identical  ENSMMUG00000014384  715GLMVGGVVIATVIVITL
Fcatus  all identical  ENSFCAG00000001556  696GLMVGGVVIATVIVITLVMLK
Mmusculus  all identical  ENSMUSG00000022892  640GLMVGGVVIATVIVITL
Ggallus  all identical  ENSGALG00000015770  696GLMVGGVVIATVIVI
Trubripes  all identical  ENSTRUG00000010470  709GLMVGGVVIATVIVITLVM
Drerio  all identical  ENSDARG00000055543  696ATVIVITLVMLRKK
Dmelanogaster  no alignment  FBgn0000108  n/a
Celegans  not conserved  C42D8.8  632PYVLASAMFITAICIIAFAITNA
Xtropicalis  all identical  ENSXETG00000013612  716GLMVGGVVIATVIVIT
protein features
start (aa)end (aa)featuredetails 
688713PEPTIDEP3(42). /FTId=PRO_0000000095.might get lost (downstream of altered splice site)
700723TRANSMEMHelical; (Potential).lost
713714SITECleavage; by gamma-secretase; site 2.might get lost (downstream of altered splice site)
717717MUTAGENV->M: Increased beta-APP42/beta-APP40 ratio. No change in apoptosis after caspase cleavage.might get lost (downstream of altered splice site)
717717MUTAGENV->C,S: Unchanged beta-APP42/total APP- beta ratio.might get lost (downstream of altered splice site)
717717MUTAGENV->F,G,I: Increased beta-APP42/beta-APP40 ratio.might get lost (downstream of altered splice site)
717717MUTAGENV->K: Decreased beta-APP42/total APP-beta ratio.might get lost (downstream of altered splice site)
720721SITECleavage; by gamma-secretase; site 3.might get lost (downstream of altered splice site)
724724CONFLICTMissing (in Ref. 22; AAB26263/AAB26264).might get lost (downstream of altered splice site)
724734MOTIFBasolateral sorting signal.might get lost (downstream of altered splice site)
724770TOPO_DOMCytoplasmic (Potential).might get lost (downstream of altered splice site)
728728MUTAGENY->A: No effect on APBA1 nor APBB1 binding. Greatly reduces the binding to APPBP2. APP internalization unchanged. No change in beta-APP42 secretion.might get lost (downstream of altered splice site)
729729MOD_RESPhosphothreonine (By similarity).might get lost (downstream of altered splice site)
730730MOD_RESPhosphoserine; by APP-kinase I (By similarity).might get lost (downstream of altered splice site)
731731CONFLICTI -> N (in Ref. 22; AAB26263/AAB26264/ AAB26265).might get lost (downstream of altered splice site)
732751REGIONInteraction with G(o)-alpha.might get lost (downstream of altered splice site)
739739MUTAGEND->A: No cleavage by caspases during apoptosis.might get lost (downstream of altered splice site)
739739MUTAGEND->N: No effect on FADD-induced apoptosis.might get lost (downstream of altered splice site)
739740SITECleavage; by caspase-6, caspase-8 or caspase-9.might get lost (downstream of altered splice site)
743743MOD_RESPhosphothreonine; by CDK5 and MAPK10.might get lost (downstream of altered splice site)
743743MUTAGENT->E: Reduced NGF-stimulated neurite extension. No effect on APP maturation.might get lost (downstream of altered splice site)
743743MUTAGENT->A: Greatly reduces the binding to SHC1 and APBB family members; no effect on NGF-stimulated neurite extension.might get lost (downstream of altered splice site)
744754HELIXmight get lost (downstream of altered splice site)
755758STRANDmight get lost (downstream of altered splice site)
756756MUTAGENG->A: APP internalization unchanged. No change in beta-APP42 secretion.might get lost (downstream of altered splice site)
757757MUTAGENY->A: Little APP internalization. Reduced beta-APP42 secretion.might get lost (downstream of altered splice site)
757757MUTAGENY->G: Loss of binding to MAPK8IP1, APBA1, APBB1, APPBP2 and SHC1.might get lost (downstream of altered splice site)
757757MOD_RESPhosphotyrosine; by ABL1 (By similarity).might get lost (downstream of altered splice site)
757757MOD_RESPhosphotyrosine.might get lost (downstream of altered splice site)
757757CONFLICTY -> S (in Ref. 30; AAA35540).might get lost (downstream of altered splice site)
759759MUTAGENN->A: No binding to APBA1, no effect on APBB1 binding. Little APP internalization. Reduced beta-APP42 secretion.might get lost (downstream of altered splice site)
759762MOTIFNPXY motif; contains endocytosis signal.might get lost (downstream of altered splice site)
760760MUTAGENP->A: Little APP internalization. Reduced beta-APP42 secretion.might get lost (downstream of altered splice site)
762762MOD_RESPhosphotyrosine.might get lost (downstream of altered splice site)
762762MUTAGENY->A: Loss of binding to APBA1 and APBB1. APP internalization unchanged. No change in beta-APP42 secretion.might get lost (downstream of altered splice site)
763765STRANDmight get lost (downstream of altered splice site)
length of protein normal
AA sequence altered yes
position of stopcodon in wt / mu CDS 2313 / 2313
position (AA) of stopcodon in wt / mu AA sequence 771 / 771
position of stopcodon in wt / mu cDNA 2347 / 2347
poly(A) signal N/A
conservation
nucleotide level for all changes - no scoring up to now		 N/A
position of start ATG in wt / mu cDNA 35 / 35
chromosome 21
strand -1
last intron/exon boundary 2246
theoretical NMD boundary in CDS 2161
length of CDS 2313
coding sequence (CDS) position 2143
cDNA position
(for ins/del: last normal base / first normal base)		 2177
gDNA position
(for ins/del: last normal base / first normal base)		 279345
chromosomal position
(for ins/del: last normal base / first normal base)		 27264102
original gDNA sequence snippet GCGGTGTTGTCATAGCGACAGTGATCGTCATCACCTTGGTG
altered gDNA sequence snippet GCGGTGTTGTCATAGCGACAATGATCGTCATCACCTTGGTG
original cDNA sequence snippet GCGGTGTTGTCATAGCGACAGTGATCGTCATCACCTTGGTG
altered cDNA sequence snippet GCGGTGTTGTCATAGCGACAATGATCGTCATCACCTTGGTG
wildtype AA sequence MLPGLALLLL AAWTARALEV PTDGNAGLLA EPQIAMFCGR LNMHMNVQNG KWDSDPSGTK
TCIDTKEGIL QYCQEVYPEL QITNVVEANQ PVTIQNWCKR GRKQCKTHPH FVIPYRCLVG
EFVSDALLVP DKCKFLHQER MDVCETHLHW HTVAKETCSE KSTNLHDYGM LLPCGIDKFR
GVEFVCCPLA EESDNVDSAD AEEDDSDVWW GGADTDYADG SEDKVVEVAE EEEVAEVEEE
EADDDEDDED GDEVEEEAEE PYEEATERTT SIATTTTTTT ESVEEVVREV CSEQAETGPC
RAMISRWYFD VTEGKCAPFF YGGCGGNRNN FDTEEYCMAV CGSAMSQSLL KTTQEPLARD
PVKLPTTAAS TPDAVDKYLE TPGDENEHAH FQKAKERLEA KHRERMSQVM REWEEAERQA
KNLPKADKKA VIQHFQEKVE SLEQEAANER QQLVETHMAR VEAMLNDRRR LALENYITAL
QAVPPRPRHV FNMLKKYVRA EQKDRQHTLK HFEHVRMVDP KKAAQIRSQV MTHLRVIYER
MNQSLSLLYN VPAVAEEIQD EVDELLQKEQ NYSDDVLANM ISEPRISYGN DALMPSLTET
KTTVELLPVN GEFSLDDLQP WHSFGADSVP ANTENEVEPV DARPAADRGL TTRPGSGLTN
IKTEEISEVK MDAEFRHDSG YEVHHQKLVF FAEDVGSNKG AIIGLMVGGV VIATVIVITL
VMLKKKQYTS IHHGVVEVDA AVTPEERHLS KMQQNGYENP TYKFFEQMQN *
mutated AA sequence MLPGLALLLL AAWTARALEV PTDGNAGLLA EPQIAMFCGR LNMHMNVQNG KWDSDPSGTK
TCIDTKEGIL QYCQEVYPEL QITNVVEANQ PVTIQNWCKR GRKQCKTHPH FVIPYRCLVG
EFVSDALLVP DKCKFLHQER MDVCETHLHW HTVAKETCSE KSTNLHDYGM LLPCGIDKFR
GVEFVCCPLA EESDNVDSAD AEEDDSDVWW GGADTDYADG SEDKVVEVAE EEEVAEVEEE
EADDDEDDED GDEVEEEAEE PYEEATERTT SIATTTTTTT ESVEEVVREV CSEQAETGPC
RAMISRWYFD VTEGKCAPFF YGGCGGNRNN FDTEEYCMAV CGSAMSQSLL KTTQEPLARD
PVKLPTTAAS TPDAVDKYLE TPGDENEHAH FQKAKERLEA KHRERMSQVM REWEEAERQA
KNLPKADKKA VIQHFQEKVE SLEQEAANER QQLVETHMAR VEAMLNDRRR LALENYITAL
QAVPPRPRHV FNMLKKYVRA EQKDRQHTLK HFEHVRMVDP KKAAQIRSQV MTHLRVIYER
MNQSLSLLYN VPAVAEEIQD EVDELLQKEQ NYSDDVLANM ISEPRISYGN DALMPSLTET
KTTVELLPVN GEFSLDDLQP WHSFGADSVP ANTENEVEPV DARPAADRGL TTRPGSGLTN
IKTEEISEVK MDAEFRHDSG YEVHHQKLVF FAEDVGSNKG AIIGLMVGGV VIATMIVITL
VMLKKKQYTS IHHGVVEVDA AVTPEERHLS KMQQNGYENP TYKFFEQMQN *
speed 0.72 s
All positions are in basepairs (bp) if not explicitly stated differently.
AA/aa: amino acid; CDS: coding sequence; mu: mutated; NMD: nonsense-mediated mRNA decay; nt: nucleotide; wt: wildtype; TGP: 1000 Genomes Project