rs141285034

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000168.6(GLI3):​c.3790G>T​(p.Ala1264Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1264T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

GLI3
NM_000168.6 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.110
Variant links:
Genes affected
GLI3 (HGNC:4319): (GLI family zinc finger 3) This gene encodes a protein which belongs to the C2H2-type zinc finger proteins subclass of the Gli family. They are characterized as DNA-binding transcription factors and are mediators of Sonic hedgehog (Shh) signaling. The protein encoded by this gene localizes in the cytoplasm and activates patched Drosophila homolog (PTCH) gene expression. It is also thought to play a role during embryogenesis. Mutations in this gene have been associated with several diseases, including Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, preaxial polydactyly type IV, and postaxial polydactyly types A1 and B. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08542937).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GLI3NM_000168.6 linkuse as main transcriptc.3790G>T p.Ala1264Ser missense_variant 15/15 ENST00000395925.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GLI3ENST00000395925.8 linkuse as main transcriptc.3790G>T p.Ala1264Ser missense_variant 15/155 NM_000168.6 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.071
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
3.6
DANN
Benign
0.66
DEOGEN2
Benign
0.26
T;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.18
N
LIST_S2
Benign
0.59
T;T
M_CAP
Benign
0.056
D
MetaRNN
Benign
0.085
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.6
L;.
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.34
T
PROVEAN
Benign
0.33
N;.
REVEL
Benign
0.046
Sift
Uncertain
0.020
D;.
Sift4G
Benign
0.78
T;.
Polyphen
0.020
B;.
Vest4
0.12
MutPred
0.16
Gain of glycosylation at A1264 (P = 0.014);.;
MVP
0.25
MPC
0.28
ClinPred
0.048
T
GERP RS
-2.6
Varity_R
0.033
gMVP
0.024

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: rs141285034; hg19: chr7-42004881; API