17-75779107-G-C
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PM5PP2PP5_Moderate
The NM_005324.5(H3-3B):c.68C>G(p.Thr23Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T23K) has been classified as Likely pathogenic.
Frequency
Consequence
NM_005324.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
H3-3B | NM_005324.5 | c.68C>G | p.Thr23Arg | missense_variant | 2/4 | ENST00000254810.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
H3-3B | ENST00000254810.8 | c.68C>G | p.Thr23Arg | missense_variant | 2/4 | 1 | NM_005324.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Bryant-Li-Bhoj neurodevelopmental syndrome 2 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Goettingen | Jan 31, 2023 | The variant c.68C>G (p.(Thr23Arg)) in exon 2 of the H3-3B-gene is not found in in the gnomAD database. Another nucleotide change resulting in another amino acid change at the same position was described as pathogenic (c.68C>A, p.(Thr23Lys); PMID: 34876591), although functional studies did not reveal a pathogenic influence of the published variant on protein function. The variant affects a highly conserved nucleotide, a highly conserved amino acid, there is a moderate physicochemical difference between Thr and Arg and the variant is located within a protein domain. This variant has a pathogenic computational verdict based on in silico prediction programs. Missense variants in H3-3B are a known mechanism of disease. It was found de novo in our patient. Thus, we consider this H3-3B-variant a likely pathogenic variant. ACMG criteria used for classification: PM2, PM5, PM6, PP2, PP3. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.