8-96145055-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_001001557.4(GDF6):āc.876G>Cā(p.Glu292Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000872 in 1,490,334 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000090 ( 0 hom. )
Consequence
GDF6
NM_001001557.4 missense
NM_001001557.4 missense
Scores
1
4
4
Clinical Significance
Conservation
PhyloP100: 0.866
Genes affected
GDF6 (HGNC:4221): (growth differentiation factor 6) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein is required for normal formation of some bones and joints in the limbs, skull, and axial skeleton. Mutations in this gene are associated with Klippel-Feil syndrome, microphthalmia, and Leber congenital amaurosis. [provided by RefSeq, Sep 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GDF6 | NM_001001557.4 | c.876G>C | p.Glu292Asp | missense_variant | 2/2 | ENST00000287020.7 | NP_001001557.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GDF6 | ENST00000287020.7 | c.876G>C | p.Glu292Asp | missense_variant | 2/2 | 1 | NM_001001557.4 | ENSP00000287020.4 |
Frequencies
GnomAD3 genomes AF: 0.00000659 AC: 1AN: 151794Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000228 AC: 3AN: 131544Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 75280
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GnomAD4 exome AF: 0.00000896 AC: 12AN: 1338540Hom.: 0 Cov.: 31 AF XY: 0.00000907 AC XY: 6AN XY: 661812
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GnomAD4 genome AF: 0.00000659 AC: 1AN: 151794Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74136
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Klippel-Feil syndrome 1, autosomal dominant;C2751307:Isolated microphthalmia 4;C3150968:Microphthalmia, isolated, with coloboma 6;C3715164:Leber congenital amaurosis 17 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 11, 2024 | - - |
Computational scores
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Name
Calibrated prediction
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Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
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Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
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D
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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