10-80157636-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_145868.2(ANXA11):c.1458+5G>A variant causes a splice region, intron change. The variant allele was found at a frequency of 0.0000385 in 1,612,116 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 predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_145868.2 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: 0.0000592 AC: 9AN: 152052Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000881 AC: 22AN: 249678Hom.: 0 AF XY: 0.0000889 AC XY: 12AN XY: 134970
GnomAD4 exome AF: 0.0000363 AC: 53AN: 1460064Hom.: 0 Cov.: 32 AF XY: 0.0000496 AC XY: 36AN XY: 726188
GnomAD4 genome AF: 0.0000592 AC: 9AN: 152052Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7AN XY: 74262
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change falls in intron 14 of the ANXA11 gene. It does not directly change the encoded amino acid sequence of the ANXA11 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs748134350, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with ANXA11-related conditions. 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 create or strengthen a 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