17-44907384-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002055.5(GFAP):āc.1262T>Cā(p.Ile421Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,088 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Consequence
GFAP
NM_002055.5 missense
NM_002055.5 missense
Scores
5
6
5
Clinical Significance
Conservation
PhyloP100: 3.75
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GFAP | NM_002055.5 | c.1262T>C | p.Ile421Thr | missense_variant | 9/9 | ENST00000588735.3 | NP_002046.1 | |
GFAP | NM_001363846.2 | c.1382T>C | p.Ile461Thr | missense_variant | 10/10 | NP_001350775.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GFAP | ENST00000588735.3 | c.1262T>C | p.Ile421Thr | missense_variant | 9/9 | 1 | NM_002055.5 | ENSP00000466598 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152088Hom.: 0 Cov.: 32
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GnomAD4 exome Cov.: 31
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 152088Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74304
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
REVEL
Pathogenic
Polyphen
B;.
MutPred
Gain of phosphorylation at I421 (P = 0.0262);.;
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at