chr15-52153937-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_016194.4(GNB5):c.375+3A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,610,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_016194.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GNB5 | NM_016194.4 | c.375+3A>G | splice_region_variant, intron_variant | Intron 4 of 12 | ENST00000261837.12 | NP_057278.2 | ||
GNB5 | NM_006578.4 | c.249+3A>G | splice_region_variant, intron_variant | Intron 2 of 10 | NP_006569.1 | |||
GNB5 | NM_001379343.1 | c.93+3A>G | splice_region_variant, intron_variant | Intron 2 of 10 | NP_001366272.1 | |||
GNB5 | XM_011521162.4 | c.249+3A>G | splice_region_variant, intron_variant | Intron 2 of 10 | XP_011519464.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250550Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135430
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1458396Hom.: 0 Cov.: 30 AF XY: 0.0000207 AC XY: 15AN XY: 725358
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74358
ClinVar
Submissions by phenotype
Gnb5-related intellectual disability-cardiac arrhythmia syndrome Pathogenic:2
Pathogenic, no assertion criteria provided | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | - | This variant was identified as compound heterozygous in an individual with devleopmental delay, intellectual disability, hypotonia, retinal dystrophy, arrhythmia. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 16, 2023 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 08, 2021 | The c.375+3A>G intronic alteration consists of a A to G substitution 3 nucleotides after exon 4 (coding exon 3) of the GNB5 gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at