rs143942705
Positions:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_000168.6(GLI3):āc.3509C>Gā(p.Ala1170Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000766 in 1,605,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00014 ( 0 hom., cov: 32)
Exomes š: 0.000070 ( 0 hom. )
Consequence
GLI3
NM_000168.6 missense
NM_000168.6 missense
Scores
1
4
14
Clinical Significance
Conservation
PhyloP100: 5.84
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 Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.027121097).
BP6
?
Variant 7-41965564-G-C is Benign according to our data. Variant chr7-41965564-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 580237.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.
BS2
?
High AC in GnomAd4 at 22 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLI3 | NM_000168.6 | c.3509C>G | p.Ala1170Gly | missense_variant | 15/15 | ENST00000395925.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLI3 | ENST00000395925.8 | c.3509C>G | p.Ala1170Gly | missense_variant | 15/15 | 5 | NM_000168.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152130Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000136 AC: 34AN: 249216Hom.: 0 AF XY: 0.000148 AC XY: 20AN XY: 135046
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GnomAD4 exome AF: 0.0000695 AC: 101AN: 1452924Hom.: 0 Cov.: 34 AF XY: 0.0000777 AC XY: 56AN XY: 720696
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GnomAD4 genome ? AF: 0.000145 AC: 22AN: 152248Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74434
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 27, 2021 | The c.3509C>G (p.A1170G) alteration is located in exon 15 (coding exon 14) of the GLI3 gene. This alteration results from a C to G substitution at nucleotide position 3509, causing the alanine (A) at amino acid position 1170 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Pallister-Hall syndrome;C0265306:Greig cephalopolysyndactyly syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Benign
T;.
Polyphen
P;.
Vest4
MVP
MPC
ClinPred
T
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