6-109465664-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001286613.2(MICAL1):c.14G>A(p.Ser5Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000071 in 1,576,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict 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_001286613.2 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152132Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000101 AC: 2AN: 197068Hom.: 0 AF XY: 0.00000932 AC XY: 1AN XY: 107290
GnomAD4 exome AF: 0.0000758 AC: 108AN: 1424480Hom.: 0 Cov.: 30 AF XY: 0.0000807 AC XY: 57AN XY: 706756
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152132Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74310
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 5 of the MICAL1 protein (p.Ser5Asn). This variant also falls at the last nucleotide of exon 1, which is part of the consensus splice site for this exon. This variant is present in population databases (rs775871899, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with MICAL1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. 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