rs267607526
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_002055.5(GFAP):c.1111G>C(p.Glu371Gln) 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: 32)
Consequence
GFAP
NM_002055.5 missense
NM_002055.5 missense
Scores
13
5
1
Clinical Significance
Conservation
PhyloP100: 7.91
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 6 ACMG points.
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 rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| GFAP | NM_002055.5 | c.1111G>C | p.Glu371Gln | missense_variant | Exon 6 of 9 | ENST00000588735.3 | NP_002046.1 | |
| GFAP | NM_001363846.2 | c.1111G>C | p.Glu371Gln | missense_variant | Exon 6 of 10 | NP_001350775.1 | ||
| GFAP | NM_001242376.3 | c.1111G>C | p.Glu371Gln | missense_variant | Exon 6 of 7 | NP_001229305.1 | ||
| GFAP | NM_001131019.3 | c.1111G>C | p.Glu371Gln | missense_variant | Exon 6 of 8 | NP_001124491.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
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
-
Epithelial Biology; Institute of Medical Biology, Singapore
Significance: not provided
Review Status: no classification provided
Collection Method: literature only
- -
Alexander disease Other:1
-
GeneReviews
Significance: not provided
Review Status: no classification provided
Collection Method: literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
.;D;.;.;.;.;.;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D;D;D;T;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
.;H;.;.;.;H;H;.;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;.;D;.;.;D;.;.;.
REVEL
Pathogenic
Sift
Uncertain
.;.;D;.;.;D;.;.;.
Sift4G
Uncertain
.;.;D;.;.;D;.;D;.
Polyphen
1.0
.;D;.;.;.;.;.;.;.
Vest4
0.87, 0.87
MutPred
Loss of ubiquitination at K368 (P = 0.0573);Loss of ubiquitination at K368 (P = 0.0573);Loss of ubiquitination at K368 (P = 0.0573);.;.;Loss of ubiquitination at K368 (P = 0.0573);Loss of ubiquitination at K368 (P = 0.0573);.;.;
MVP
1.0
MPC
1.2
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