chr17-75778629-T-C
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM1PM2PM5PP2PP3PP5_Very_Strong
The NM_005324.5(H3-3B):c.377A>G(p.Gln126Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. Q126K) has been classified as Likely pathogenic.
Frequency
Consequence
NM_005324.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
H3-3B | NM_005324.5 | c.377A>G | p.Gln126Arg | missense_variant | 4/4 | ENST00000254810.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
H3-3B | ENST00000254810.8 | c.377A>G | p.Gln126Arg | missense_variant | 4/4 | 1 | NM_005324.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Bryant-Li-Bhoj neurodevelopmental syndrome 2 Pathogenic:4
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratoire de Génétique Moléculaire, CHU Bordeaux | Mar 03, 2022 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 02, 2022 | - - |
Pathogenic, criteria provided, single submitter | research | Laboratory of Medical Genetics, University of Torino | Nov 29, 2022 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | 3billion | May 22, 2022 | The variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.72; 3Cnet: 3CNET). The variant has been previously reported as de novo in a similarly affected individual (PMID: 33268356). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. - |
H3-3B-related disorder Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 26, 2023 | The H3-3B c.377A>G variant is predicted to result in the amino acid substitution p.Gln126Arg. This variant was reported as de novo in a patient with neurodegenerative disease with features of developmental delay, brain abnormalities, seizures, hypotonia, strabismus, hypertelorism and constipation (Table S1, Bryant. 2020. PubMed ID: 33268356). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as likely pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.