mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999999999965 (explain)

Summary

amino acid sequence changed
known as potential disease variant: rs18094 (probable pathogenic)
known disease mutation at this position (HGMD CM930033)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr21:27264108C>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.2137G>A
cDNA.2171G>A
g.279339G>A

AA changes

A713T Score: 58 explain score(s)

position(s) of altered AA
if AA alteration in CDS

713

frameshift

known variant

Reference ID: rs63750066

database	homozygous (T/T)	heterozygous	allele carriers
1000G	0	1	1
ExAC	0	7	7

known as potential disease variant: rs18094 (probable pathogenic for Alzheimer disease|Alzheimer disease, type 1|Primary degenerative dementia of the Alzheimer type, presenile onset|not provided) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)

known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)
known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	5.732	1
	5.732	1
(flanking)	2.113	1

explain score(s) and/or inspect your position(s) in in UCSC Genome Browser

splice sites

effect	gDNA position	score	wt detection sequence	exon-intron border
Donor marginally increased	279344	wt: 0.7349 / mu: 0.7640 (marginal change - not scored)	wt: GCGACAGTGATCGTC mu: ACGACAGTGATCGTC	GACA\|gtga
Donor gained	279339	0.76	mu: TCATAACGACAGTGA	ATAA\|cgac
Donor gained	279340	0.35	mu: CATAACGACAGTGAT	TAAC\|gaca

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

713

mutated

not conserved

713

Ptroglodytes

all identical

ENSPTRG00000013811

713

Mmulatta

all identical

ENSMMUG00000014384

713

Fcatus

all identical

ENSFCAG00000001556

694

Mmusculus

all identical

ENSMUSG00000022892

638

Ggallus

all identical

ENSGALG00000015770

694

Trubripes

all identical

ENSTRUG00000010470

707

Drerio

all identical

ENSDARG00000055543

694

Dmelanogaster

no alignment

FBgn0000108

n/a

Celegans

not conserved

C42D8.8

630

Xtropicalis

all identical

ENSXETG00000013612

714

protein features

start (aa)	end (aa)	feature	details
688	713	PEPTIDE	P3(42). /FTId=PRO_0000000095.	lost
700	723	TRANSMEM	Helical; (Potential).	lost
713	714	SITE	Cleavage; by gamma-secretase; site 2.	lost
717	717	MUTAGEN	V->M: Increased beta-APP42/beta-APP40 ratio. No change in apoptosis after caspase cleavage.	might get lost (downstream of altered splice site)
717	717	MUTAGEN	V->C,S: Unchanged beta-APP42/total APP- beta ratio.	might get lost (downstream of altered splice site)
717	717	MUTAGEN	V->F,G,I: Increased beta-APP42/beta-APP40 ratio.	might get lost (downstream of altered splice site)
717	717	MUTAGEN	V->K: Decreased beta-APP42/total APP-beta ratio.	might get lost (downstream of altered splice site)
720	721	SITE	Cleavage; by gamma-secretase; site 3.	might get lost (downstream of altered splice site)
724	724	CONFLICT	Missing (in Ref. 22; AAB26263/AAB26264).	might get lost (downstream of altered splice site)
724	734	MOTIF	Basolateral sorting signal.	might get lost (downstream of altered splice site)
724	770	TOPO_DOM	Cytoplasmic (Potential).	might get lost (downstream of altered splice site)
728	728	MUTAGEN	Y->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)
729	729	MOD_RES	Phosphothreonine (By similarity).	might get lost (downstream of altered splice site)
730	730	MOD_RES	Phosphoserine; by APP-kinase I (By similarity).	might get lost (downstream of altered splice site)
731	731	CONFLICT	I -> N (in Ref. 22; AAB26263/AAB26264/ AAB26265).	might get lost (downstream of altered splice site)
732	751	REGION	Interaction with G(o)-alpha.	might get lost (downstream of altered splice site)
739	739	MUTAGEN	D->A: No cleavage by caspases during apoptosis.	might get lost (downstream of altered splice site)
739	739	MUTAGEN	D->N: No effect on FADD-induced apoptosis.	might get lost (downstream of altered splice site)
739	740	SITE	Cleavage; by caspase-6, caspase-8 or caspase-9.	might get lost (downstream of altered splice site)
743	743	MOD_RES	Phosphothreonine; by CDK5 and MAPK10.	might get lost (downstream of altered splice site)
743	743	MUTAGEN	T->E: Reduced NGF-stimulated neurite extension. No effect on APP maturation.	might get lost (downstream of altered splice site)
743	743	MUTAGEN	T->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)
744	754	HELIX		might get lost (downstream of altered splice site)
755	758	STRAND		might get lost (downstream of altered splice site)
756	756	MUTAGEN	G->A: APP internalization unchanged. No change in beta-APP42 secretion.	might get lost (downstream of altered splice site)
757	757	MUTAGEN	Y->A: Little APP internalization. Reduced beta-APP42 secretion.	might get lost (downstream of altered splice site)
757	757	MUTAGEN	Y->G: Loss of binding to MAPK8IP1, APBA1, APBB1, APPBP2 and SHC1.	might get lost (downstream of altered splice site)
757	757	MOD_RES	Phosphotyrosine; by ABL1 (By similarity).	might get lost (downstream of altered splice site)
757	757	MOD_RES	Phosphotyrosine.	might get lost (downstream of altered splice site)
757	757	CONFLICT	Y -> S (in Ref. 30; AAA35540).	might get lost (downstream of altered splice site)
759	759	MUTAGEN	N->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)
759	762	MOTIF	NPXY motif; contains endocytosis signal.	might get lost (downstream of altered splice site)
760	760	MUTAGEN	P->A: Little APP internalization. Reduced beta-APP42 secretion.	might get lost (downstream of altered splice site)
762	762	MOD_RES	Phosphotyrosine.	might get lost (downstream of altered splice site)
762	762	MUTAGEN	Y->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)
763	765	STRAND		might 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

strand

-1

last intron/exon boundary

2246

theoretical NMD boundary in CDS

2161

length of CDS

2313

coding sequence (CDS) position

2137

cDNA position
(for ins/del: last normal base / first normal base)

2171

gDNA position
(for ins/del: last normal base / first normal base)

279339

chromosomal position
(for ins/del: last normal base / first normal base)

27264108

original gDNA sequence snippet

TGGTGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACC

altered gDNA sequence snippet

TGGTGGGCGGTGTTGTCATAACGACAGTGATCGTCATCACC

original cDNA sequence snippet

TGGTGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACC

altered cDNA sequence snippet

TGGTGGGCGGTGTTGTCATAACGACAGTGATCGTCATCACC

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 VITTVIVITL
VMLKKKQYTS IHHGVVEVDA AVTPEERHLS KMQQNGYENP TYKFFEQMQN *

speed

0.16 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