rs488890
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001080467.3(MYO5B):c.4315+5G>T variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000374 in 1,603,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001080467.3 splice_donor_5th_base, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO5B | NM_001080467.3 | c.4315+5G>T | splice_donor_5th_base_variant, intron_variant | ENST00000285039.12 | |||
SNHG22 | NR_117096.1 | n.193-75C>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO5B | ENST00000285039.12 | c.4315+5G>T | splice_donor_5th_base_variant, intron_variant | 1 | NM_001080467.3 | P1 | |||
SNHG22 | ENST00000589499.1 | n.193-75C>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151990Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249532Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135386
GnomAD4 exome AF: 0.00000345 AC: 5AN: 1451358Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 722688
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151990Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74212
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | This sequence change falls in intron 32 of the MYO5B gene. It does not directly change the encoded amino acid sequence of the MYO5B protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs488890, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with MYO5B-related conditions. ClinVar contains an entry for this variant (Variation ID: 1488873). 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 is not likely to affect RNA splicing. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at