7-155802871-T-C
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
The NM_000193.4(SHH):c.*29A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.020 ( 0 hom., cov: 0)
Exomes 𝑓: 0.30 ( 5 hom. )
Failed GnomAD Quality Control
Consequence
SHH
NM_000193.4 3_prime_UTR
NM_000193.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.79
Genes affected
SHH (HGNC:10848): (sonic hedgehog signaling molecule) This gene encodes a protein that is instrumental in patterning the early embryo. It has been implicated as the key inductive signal in patterning of the ventral neural tube, the anterior-posterior limb axis, and the ventral somites. Of three human proteins showing sequence and functional similarity to the sonic hedgehog protein of Drosophila, this protein is the most similar. The protein is made as a precursor that is autocatalytically cleaved; the N-terminal portion is soluble and contains the signalling activity while the C-terminal portion is involved in precursor processing. More importantly, the C-terminal product covalently attaches a cholesterol moiety to the N-terminal product, restricting the N-terminal product to the cell surface and preventing it from freely diffusing throughout the developing embryo. Defects in this protein or in its signalling pathway are a cause of holoprosencephaly (HPE), a disorder in which the developing forebrain fails to correctly separate into right and left hemispheres. HPE is manifested by facial deformities. It is also thought that mutations in this gene or in its signalling pathway may be responsible for VACTERL syndrome, which is characterized by vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, radial and renal dysplasia, cardiac anomalies, and limb abnormalities. Additionally, mutations in a long range enhancer located approximately 1 megabase upstream of this gene disrupt limb patterning and can result in preaxial polydactyly. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 7-155802871-T-C is Benign according to our data. Variant chr7-155802871-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1200869.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SHH | NM_000193.4 | c.*29A>G | 3_prime_UTR_variant | 3/3 | ENST00000297261.7 | NP_000184.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SHH | ENST00000297261 | c.*29A>G | 3_prime_UTR_variant | 3/3 | 1 | NM_000193.4 | ENSP00000297261.2 | |||
SHH | ENST00000430104.5 | c.302-2626A>G | intron_variant | 1 | ENSP00000396621.1 | |||||
SHH | ENST00000435425.1 | n.302-2274A>G | intron_variant | 1 | ENSP00000413871.1 | |||||
SHH | ENST00000441114.5 | n.302-2204A>G | intron_variant | 1 | ENSP00000410546.1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 895AN: 44274Hom.: 0 Cov.: 0 FAILED QC
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GnomAD3 exomes AF: 0.0290 AC: 335AN: 11538Hom.: 0 AF XY: 0.0296 AC XY: 199AN XY: 6732
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.302 AC: 53314AN: 176720Hom.: 5 Cov.: 5 AF XY: 0.293 AC XY: 25921AN XY: 88324
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0202 AC: 897AN: 44324Hom.: 0 Cov.: 0 AF XY: 0.0192 AC XY: 444AN XY: 23182
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 23, 2019 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at