rs104894040
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PM5PP3_StrongPP5
The NM_000193.4(SHH):c.349T>G(p.Trp117Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/20 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W117R) has been classified as Pathogenic.
Frequency
Consequence
NM_000193.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SHH | NM_000193.4 | c.349T>G | p.Trp117Gly | missense_variant | 2/3 | ENST00000297261.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SHH | ENST00000297261.7 | c.349T>G | p.Trp117Gly | missense_variant | 2/3 | 1 | NM_000193.4 | P1 | |
SHH | ENST00000430104.5 | c.88T>G | p.Trp30Gly | missense_variant | 3/4 | 1 | |||
SHH | ENST00000441114.5 | c.88T>G | p.Trp30Gly | missense_variant, NMD_transcript_variant | 3/5 | 1 | |||
SHH | ENST00000435425.1 | c.88T>G | p.Trp30Gly | missense_variant, NMD_transcript_variant | 3/5 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD4 exome Cov.: 34
GnomAD4 genome ? Cov.: 34
ClinVar
Submissions by phenotype
Holoprosencephaly 3 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 22, 2005 | - - |
Pathogenic, no assertion criteria provided | curation | GeneReviews | Aug 29, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at