rs267607501
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3
The NM_002055.5(GFAP):c.256_259delinsGAGT(p.Lys86_Val87delinsGluPhe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
GFAP
NM_002055.5 missense
NM_002055.5 missense
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.73
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 Uncertain_significance. Variant got 5 ACMG points.
PM1
In a hotspot region, there are 6 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 9 uncertain in NM_002055.5
PM2
Very rare variant in population databases, with high coverage;
PP3
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GFAP | NM_002055.5 | c.256_259delinsGAGT | p.Lys86_Val87delinsGluPhe | missense_variant | 1/9 | ENST00000588735.3 | |
GFAP | NM_001131019.3 | c.256_259delinsGAGT | p.Lys86_Val87delinsGluPhe | missense_variant | 1/8 | ||
GFAP | NM_001242376.3 | c.256_259delinsGAGT | p.Lys86_Val87delinsGluPhe | missense_variant | 1/7 | ||
GFAP | NM_001363846.2 | c.256_259delinsGAGT | p.Lys86_Val87delinsGluPhe | missense_variant | 1/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GFAP | ENST00000588735.3 | c.256_259delinsGAGT | p.Lys86_Val87delinsGluPhe | missense_variant | 1/9 | 1 | NM_002055.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
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
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at