X-19537712-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_031892.3(SH3KBP1):c.1956+5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000663 in 1,206,176 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_031892.3 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000179 AC: 2AN: 111470Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33630
GnomAD3 exomes AF: 0.00000545 AC: 1AN: 183331Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67763
GnomAD4 exome AF: 0.00000548 AC: 6AN: 1094706Hom.: 0 Cov.: 28 AF XY: 0.00000833 AC XY: 3AN XY: 360222
GnomAD4 genome AF: 0.0000179 AC: 2AN: 111470Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33630
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 27, 2023 | This variant has not been reported in the literature in individuals affected with SH3KBP1-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant is present in population databases (no rsID available, gnomAD 0.004%). This sequence change falls in intron 17 of the SH3KBP1 gene. It does not directly change the encoded amino acid sequence of the SH3KBP1 protein. It affects a nucleotide within the consensus splice site. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at