17-44907369-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002055.5(GFAP):​c.1277A>T​(p.Gln426Leu) variant causes a missense change. 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

Scores

5
8
3

Clinical Significance

not provided no classification provided O:2

Conservation

PhyloP100: 5.57
Variant links:
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
GFAPNM_002055.5 linkuse as main transcriptc.1277A>T p.Gln426Leu missense_variant 9/9 ENST00000588735.3 NP_002046.1
GFAPNM_001363846.2 linkuse as main transcriptc.1397A>T p.Gln466Leu missense_variant 10/10 NP_001350775.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GFAPENST00000588735.3 linkuse as main transcriptc.1277A>T p.Gln426Leu missense_variant 9/91 NM_002055.5 ENSP00000466598 P1P14136-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
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 providedliterature onlyEpithelial Biology; Institute of Medical Biology, Singapore-- -
Alexander disease Other:1
not provided, no classification providedliterature onlyGeneReviews-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Pathogenic
0.36
D
BayesDel_noAF
Pathogenic
0.28
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.66
D;.
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.86
D;T
M_CAP
Pathogenic
0.39
D
MetaRNN
Uncertain
0.72
D;D
MetaSVM
Pathogenic
0.98
D
MutationAssessor
Uncertain
2.3
M;.
MutationTaster
Benign
0.79
D;D
PrimateAI
Benign
0.48
T
REVEL
Pathogenic
0.78
Polyphen
0.76
P;.
MutPred
0.35
Gain of catalytic residue at Q426 (P = 0.0032);.;
MVP
1.0
ClinPred
0.98
D
GERP RS
4.3
Varity_R
0.39
gMVP
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs267607521; hg19: chr17-42984737; API