10-80157636-C-T
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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 donor 5th base, 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
Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
ANXA11
NM_145868.2 splice_donor_5th_base, intron
NM_145868.2 splice_donor_5th_base, intron
Scores
2
Splicing: ADA: 0.9997
2
Clinical Significance
Conservation
PhyloP100: 5.87
Genes affected
ANXA11 (HGNC:535): (annexin A11) This gene encodes a member of the annexin family, a group of calcium-dependent phospholipid-binding proteins. Annexins have unique N-terminal domains and conserved C-terminal domains, which contain calcium-dependent phospholipid-binding sites. The encoded protein is a 56-kD antigen recognized by sera from patients with various autoimmune diseases. Several transcript variants encoding two different isoforms have been identified. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAd4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANXA11 | NM_145868.2 | c.1458+5G>A | splice_donor_5th_base_variant, intron_variant | ENST00000422982.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANXA11 | ENST00000422982.8 | c.1458+5G>A | splice_donor_5th_base_variant, intron_variant | 1 | NM_145868.2 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152052Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000881 AC: 22AN: 249678Hom.: 0 AF XY: 0.0000889 AC XY: 12AN XY: 134970
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GnomAD4 exome AF: 0.0000363 AC: 53AN: 1460064Hom.: 0 Cov.: 32 AF XY: 0.0000496 AC XY: 36AN XY: 726188
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GnomAD4 genome AF: 0.0000592 AC: 9AN: 152052Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7AN XY: 74262
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 10, 2023 | 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
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at