rs746870989
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP3BP6_Moderate
The NM_000168.6(GLI3):c.847A>T(p.Arg283Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
GLI3
NM_000168.6 missense
NM_000168.6 missense
Scores
11
7
1
Clinical Significance
Conservation
PhyloP100: 3.23
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 Likely_benign. Variant got -1 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.814
BP6
?
Variant 7-42040219-T-A is Benign according to our data. Variant chr7-42040219-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 528806.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLI3 | NM_000168.6 | c.847A>T | p.Arg283Trp | missense_variant | 7/15 | ENST00000395925.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLI3 | ENST00000395925.8 | c.847A>T | p.Arg283Trp | missense_variant | 7/15 | 5 | NM_000168.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251400Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135876
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1460364Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726604
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74322
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Pallister-Hall syndrome;C0265306:Greig cephalopolysyndactyly syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 02, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Pathogenic
DEOGEN2
Pathogenic
D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D
PrimateAI
Pathogenic
T
PROVEAN
Pathogenic
D;.
REVEL
Uncertain
Sift
Pathogenic
D;.
Sift4G
Pathogenic
D;.
Polyphen
D;.
Vest4
MutPred
Loss of methylation at R287 (P = 0.031);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Score
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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