chr7-41961971-TA-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1
The NM_000168.6(GLI3):c.*2358del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0301 in 136,184 control chromosomes in the GnomAD database, including 65 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.030 ( 65 hom., cov: 32)
Exomes 𝑓: 0.17 ( 0 hom. )
Consequence
GLI3
NM_000168.6 3_prime_UTR
NM_000168.6 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.972
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 -8 ACMG points.
BA1
GnomAdExome4 highest population allele frequency = 0.167 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLI3 | NM_000168.6 | c.*2358del | 3_prime_UTR_variant | 15/15 | ENST00000395925.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLI3 | ENST00000395925.8 | c.*2358del | 3_prime_UTR_variant | 15/15 | 5 | NM_000168.6 | P1 | ||
GLI3 | ENST00000677288.1 | c.*2358del | 3_prime_UTR_variant | 14/14 | |||||
GLI3 | ENST00000677605.1 | c.*2358del | 3_prime_UTR_variant | 15/15 | P1 | ||||
GLI3 | ENST00000678429.1 | c.*2358del | 3_prime_UTR_variant | 15/15 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0301 AC: 4097AN: 136108Hom.: 65 Cov.: 32
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GnomAD4 exome AF: 0.167 AC: 1AN: 6Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 1AN XY: 6
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GnomAD4 genome AF: 0.0301 AC: 4101AN: 136178Hom.: 65 Cov.: 32 AF XY: 0.0302 AC XY: 1987AN XY: 65780
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Greig cephalopolysyndactyly syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Polydactyly Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Pallister-Hall syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 12, 2021 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at