17-44911375-G-C

Variant summary

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

The NM_002055.5(GFAP):​c.988C>G​(p.Arg330Gly) 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

3
9
7

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 4.85
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]

Genome browser will be placed here

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.988C>G p.Arg330Gly missense_variant 6/9 ENST00000588735.3 NP_002046.1 P14136-1
GFAPNM_001363846.2 linkuse as main transcriptc.988C>G p.Arg330Gly missense_variant 6/10 NP_001350775.1
GFAPNM_001242376.3 linkuse as main transcriptc.988C>G p.Arg330Gly missense_variant 6/7 NP_001229305.1 P14136-2
GFAPNM_001131019.3 linkuse as main transcriptc.988C>G p.Arg330Gly missense_variant 6/8 NP_001124491.1 P14136-3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GFAPENST00000588735.3 linkuse as main transcriptc.988C>G p.Arg330Gly missense_variant 6/91 NM_002055.5 ENSP00000466598.2 P14136-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: not provided
Submissions summary: Other:1
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-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.060
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.75
.;D;.;.;.;.
Eigen
Benign
0.13
Eigen_PC
Benign
0.073
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.82
T;T;T;T;T;T
M_CAP
Pathogenic
0.31
D
MetaRNN
Uncertain
0.74
D;D;D;D;D;D
MetaSVM
Uncertain
0.16
D
MutationAssessor
Benign
1.5
.;L;.;.;L;L
MutationTaster
Benign
0.97
D;D;D;D
PrimateAI
Benign
0.45
T
PROVEAN
Pathogenic
-5.0
.;.;D;.;D;.
REVEL
Uncertain
0.62
Sift
Uncertain
0.015
.;.;D;.;D;.
Sift4G
Uncertain
0.041
.;.;D;.;D;.
Polyphen
0.62
.;P;.;.;.;.
Vest4
0.71, 0.71
MutPred
0.61
Loss of stability (P = 0.0665);Loss of stability (P = 0.0665);Loss of stability (P = 0.0665);.;Loss of stability (P = 0.0665);Loss of stability (P = 0.0665);
MVP
0.98
ClinPred
0.99
D
GERP RS
2.3
Varity_R
0.61
gMVP
0.96

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: rs267607513; hg19: chr17-42988743; API