rs58536923
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_002055.5(GFAP):c.835A>G(p.Lys279Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
GFAP
NM_002055.5 missense
NM_002055.5 missense
Scores
7
5
1
Clinical Significance
Conservation
PhyloP100: 8.02
Genes affected
GFAP (HGNC:4235): (glial fibrillary acidic protein) This gene encodes one of the major intermediate filament proteins of mature astrocytes. It is used as a marker to distinguish astrocytes from other glial cells during development. Mutations in this gene cause Alexander disease, a rare disorder of astrocytes in the central nervous system. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM1
?
In a region_of_interest Coil 2B (size 120) in uniprot entity GFAP_HUMAN there are 27 pathogenic changes around while only 6 benign (82%) in NM_002055.5
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.979
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GFAP | NM_002055.5 | c.835A>G | p.Lys279Glu | missense_variant | 5/9 | ENST00000588735.3 | |
GFAP | NM_001363846.2 | c.835A>G | p.Lys279Glu | missense_variant | 5/10 | ||
GFAP | NM_001242376.3 | c.835A>G | p.Lys279Glu | missense_variant | 5/7 | ||
GFAP | NM_001131019.3 | c.835A>G | p.Lys279Glu | missense_variant | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GFAP | ENST00000588735.3 | c.835A>G | p.Lys279Glu | missense_variant | 5/9 | 1 | NM_002055.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: not provided
Submissions summary: Other:2
Revision: no classification provided
LINK: link
Submissions by phenotype
not provided Other:1
not provided, no classification provided | literature only | Epithelial Biology; Institute of Medical Biology, Singapore | - | - - |
Alexander disease Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
Polyphen
1.0
.;D;.;.;.;.;.;.;.
Vest4
0.87, 0.86, 0.93
MutPred
Loss of MoRF binding (P = 0.0024);Loss of MoRF binding (P = 0.0024);Loss of MoRF binding (P = 0.0024);.;Loss of MoRF binding (P = 0.0024);Loss of MoRF binding (P = 0.0024);Loss of MoRF binding (P = 0.0024);.;.;
MVP
1.0
MPC
1.4
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at