Prediction |
disease causing |
Model: simple_aae, prob: 0.999999999879803 (classification due to ClinVar,
real probability is shown anyway)
(explain) |
| Summary |
- amino acid sequence changed
- known disease mutation at this position (HGMD CM980054)
- known disease mutation: rs4003 (pathogenic)
- protein features (might be) affected
- splice site changes
|
hyperlink |
| analysed issue |
analysis result |
| name of alteration | no title |
| alteration (phys. location) | chr1:19203992G>AN/A
show variant in all transcripts IGV
|
| HGNC symbol | ALDH4A1 |
| Ensembl transcript ID | ENST00000538309 |
| Genbank transcript ID | NM_001161504 |
| UniProt peptide | P30038 |
| alteration type | single base exchange |
| alteration region | CDS |
| DNA changes | c.875C>T
cDNA.1191C>T
g.25284C>T |
| AA changes | S292L Score: 145 explain score(s) |
position(s) of altered AA
if AA alteration in CDS | 292 |
| frameshift | no |
| known variant | Reference ID: rs137852937
| database | homozygous (A/A) | heterozygous | allele carriers |
| 1000G | - | - | - |
| ExAC | 0 | 11 | 11 |
known disease mutation: rs4003 (pathogenic for Deficiency of pyrroline-5-carboxylate reductase) dbSNP
NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM980054)
known disease mutation at this position, please check HGMD for details (HGMD ID CM980054)
known disease mutation at this position, please check HGMD for details (HGMD ID CM980054)
|
| regulatory features | H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation |
| phyloP / phastCons | | PhyloP | PhastCons |
| (flanking) | -0.279 | 0.964 | | 4.923 | 1 | | (flanking) | 4.08 | 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 | | Acc increased | 25286 | wt: 0.36 / mu: 0.56 | wt: AGAAGTGTTCCGCGTGCTCGCGTCTCTACGTGCCGCACTCG
mu: AGAAGTGTTCCGCGTGCTTGCGTCTCTACGTGCCGCACTCG | tcgc|GTCT | | Acc increased | 25292 | wt: 0.30 / mu: 0.43 | wt: GTTCCGCGTGCTCGCGTCTCTACGTGCCGCACTCGCTGTGG
mu: GTTCCGCGTGCTTGCGTCTCTACGTGCCGCACTCGCTGTGG | ctct|ACGT | | Donor marginally increased | 25289 | wt: 0.6604 / mu: 0.6873 (marginal change - not scored) | wt: CGCGTCTCTACGTGC
mu: TGCGTCTCTACGTGC | CGTC|tcta |
|
| distance from splice site | 83 |
| Kozak consensus sequence altered? | N/A |
conservation
protein level for non-synonymous changes | | species | match | gene | aa | alignment | | Human | | | 292 | F | E | Y | G | G | Q | K | C | S | A | C | S | R | L | Y | V | P | H | S | L | W | P | Q | I |
| mutated | not conserved | | 292 | F | E | Y | G | G | Q | K | C | S | A | C | L | R | L | Y | V | P | H | S | L | | | |
| Ptroglodytes | all identical | ENSPTRG00000000255 | 352 | F | E | Y | G | G | Q | K | C | S | A | C | S | R | L | Y | V | P | H | S | L | W | | |
| Mmulatta | all identical | ENSMMUG00000004751 | 219 | F | E | Y | G | G | Q | K | C | S | A | C | S | R | L | Y | V | P | H | S | L | W | P | Q |
| Fcatus | all identical | ENSFCAG00000008767 | 351 | F | E | Y | G | G | Q | K | C | S | A | C | S | R | L | Y | V | P | Q | S | L | W | | |
| Mmusculus | all identical | ENSMUSG00000028737 | 351 | F | E | Y | G | G | Q | K | C | S | A | C | S | R | L | Y | V | P | K | S | L | | | |
| Ggallus | all identical | ENSGALG00000003804 | 340 | F | E | Y | G | G | Q | K | C | S | A | C | S | R | L | Y | A | P | R | S | L | W | | |
| Trubripes | no homologue | | | |
| Drerio | all identical | ENSDARG00000038207 | 345 | F | E | Y | G | G | Q | K | C | S | A | C | S | R | M | Y | V | P | D | S | L | W | | |
| Dmelanogaster | all identical | FBgn0037138 | 363 | F | E | Y | C | G | Q | K | C | S | A | C | S | R | M | Y | V | P | E | S | | | | |
| Celegans | all identical | F56D12.1 | 352 | W | E | Y | S | G | Q | K | C | S | A | C | S | R | M | Y | A | P | K | S | I | W | P | K |
| Xtropicalis | all identical | ENSXETG00000018531 | 328 | M | E | T | V | G | Q | - | - | D | G | D | S | R | A | R | W | R | H | R | T | R | | |
|
| protein features | | start (aa) | end (aa) | feature | details | | | 288 | 300 | HELIX | | lost | | 302 | 304 | HELIX | | might get lost (downstream of altered splice site) | | 310 | 314 | STRAND | | might get lost (downstream of altered splice site) | | 314 | 314 | ACT_SITE | Proton acceptor (By similarity). | might get lost (downstream of altered splice site) | | 319 | 323 | STRAND | | might get lost (downstream of altered splice site) | | 329 | 341 | HELIX | | might get lost (downstream of altered splice site) | | 342 | 345 | HELIX | | might get lost (downstream of altered splice site) | | 348 | 348 | ACT_SITE | Nucleophile. | might get lost (downstream of altered splice site) | | 351 | 357 | STRAND | | might get lost (downstream of altered splice site) | | 352 | 352 | MUTAGEN | S->A: Reduced affinity for NAD. No effect on enzyme activity. | might get lost (downstream of altered splice site) | | 354 | 354 | CONFLICT | L -> K (in Ref. 9; AA sequence). | might get lost (downstream of altered splice site) | | 358 | 360 | HELIX | | might get lost (downstream of altered splice site) | | 361 | 373 | HELIX | | might get lost (downstream of altered splice site) | | 376 | 376 | CONFLICT | K -> R (in Ref. 3; BAD96206). | might get lost (downstream of altered splice site) | | 380 | 382 | TURN | | might get lost (downstream of altered splice site) | | 394 | 409 | HELIX | | might get lost (downstream of altered splice site) | | 402 | 402 | MOD_RES | N6-acetyllysine (By similarity). | might get lost (downstream of altered splice site) | | 413 | 417 | STRAND | | might get lost (downstream of altered splice site) | | 424 | 426 | STRAND | | might get lost (downstream of altered splice site) | | 432 | 437 | STRAND | | might get lost (downstream of altered splice site) | | 442 | 445 | HELIX | | might get lost (downstream of altered splice site) | | 447 | 447 | BINDING | NAD (By similarity). | might get lost (downstream of altered splice site) | | 450 | 458 | STRAND | | might get lost (downstream of altered splice site) | | 460 | 462 | HELIX | | might get lost (downstream of altered splice site) | | 463 | 473 | HELIX | | might get lost (downstream of altered splice site) | | 474 | 483 | STRAND | | might get lost (downstream of altered splice site) | | 487 | 496 | HELIX | | might get lost (downstream of altered splice site) | | 497 | 500 | TURN | | might get lost (downstream of altered splice site) | | 502 | 508 | STRAND | | might get lost (downstream of altered splice site) | | 505 | 505 | MOD_RES | Phosphotyrosine. | might get lost (downstream of altered splice site) | | 513 | 513 | BINDING | Substrate (By similarity). | might get lost (downstream of altered splice site) | | 515 | 517 | TURN | | might get lost (downstream of altered splice site) | | 524 | 526 | CONFLICT | RAS -> GSA (in Ref. 9; AA sequence). | might get lost (downstream of altered splice site) | | 534 | 536 | STRAND | | might get lost (downstream of altered splice site) | | 537 | 541 | HELIX | | might get lost (downstream of altered splice site) | | 542 | 550 | STRAND | | might get lost (downstream of altered splice site) | | 560 | 562 | HELIX | | might get lost (downstream of altered splice site) |
|
| length of protein | normal |
| AA sequence altered | yes |
| position of stopcodon in wt / mu CDS | 1512 / 1512 |
| position (AA) of stopcodon in wt / mu AA sequence | 504 / 504 |
| position of stopcodon in wt / mu cDNA | 1828 / 1828 |
| 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 | 317 / 317 |
| chromosome | 1 |
| strand | -1 |
| last intron/exon boundary | 1716 |
| theoretical NMD boundary in CDS | 1349 |
| length of CDS | 1512 |
| coding sequence (CDS) position | 875 |
cDNA position
(for ins/del: last normal base / first normal base) | 1191 |
gDNA position
(for ins/del: last normal base / first normal base) | 25284 |
chromosomal position
(for ins/del: last normal base / first normal base) | 19203992 |
| original gDNA sequence snippet | CCAGAAGTGTTCCGCGTGCTCGCGTCTCTACGTGCCGCACT |
| altered gDNA sequence snippet | CCAGAAGTGTTCCGCGTGCTTGCGTCTCTACGTGCCGCACT |
| original cDNA sequence snippet | CCAGAAGTGTTCCGCGTGCTCGCGTCTCTACGTGCCGCACT |
| altered cDNA sequence snippet | CCAGAAGTGTTCCGCGTGCTTGCGTCTCTACGTGCCGCACT |
| wildtype AA sequence | MEAIPCVVGD EEVWTSDVQY QVSPFNHGHK VAKFCYADKS LLNKAIEAAL AARKEWDLKP
IADRAQIFLK AADMLSGPRR AEILAKTMVG QGKTVIQAEI DAAAELIDFF RFNAKYAVEL
EGQQPISVPP STNSTVYRGL EGFVAAISPF NFTAIGGNLA GAPALMGNVV LWKPSDTAML
ASYAVYRILR EAGLPPNIIQ FVPADGPLFG DTVTSSEHLC GINFTGSVPT FKHLWKQVAQ
NLDRFHTFPR LAGECGGKNF HFVHRSADVE SVVSGTLRSA FEYGGQKCSA CSRLYVPHSL
WPQIKGRLLE EHSRIKVGDP AEDFGTFFSA VIDAKSFARI KKWLEHARSS PSLTILAGGK
CDDSVGYFVE PCIVESKDPQ EPIMKEEIFG PVLSVYVYPD DKYKETLQLV DSTTSYGLTG
AVFSQDKDVV QEATKVLRNA AGNFYINDKS TGSIVGQQPF GGARASGTND KPGGPHYILR
WTSPQVIKET HKPLGDWSYA YMQ* |
| mutated AA sequence | MEAIPCVVGD EEVWTSDVQY QVSPFNHGHK VAKFCYADKS LLNKAIEAAL AARKEWDLKP
IADRAQIFLK AADMLSGPRR AEILAKTMVG QGKTVIQAEI DAAAELIDFF RFNAKYAVEL
EGQQPISVPP STNSTVYRGL EGFVAAISPF NFTAIGGNLA GAPALMGNVV LWKPSDTAML
ASYAVYRILR EAGLPPNIIQ FVPADGPLFG DTVTSSEHLC GINFTGSVPT FKHLWKQVAQ
NLDRFHTFPR LAGECGGKNF HFVHRSADVE SVVSGTLRSA FEYGGQKCSA CLRLYVPHSL
WPQIKGRLLE EHSRIKVGDP AEDFGTFFSA VIDAKSFARI KKWLEHARSS PSLTILAGGK
CDDSVGYFVE PCIVESKDPQ EPIMKEEIFG PVLSVYVYPD DKYKETLQLV DSTTSYGLTG
AVFSQDKDVV QEATKVLRNA AGNFYINDKS TGSIVGQQPF GGARASGTND KPGGPHYILR
WTSPQVIKET HKPLGDWSYA YMQ* |
| speed | 0.73 s |
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