10-60042695-G-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_020987.5(ANK3):c.13130C>T(p.Ser4377Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000521 in 1,613,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_020987.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000461 AC: 7AN: 151940Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000115 AC: 29AN: 251392Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135862
GnomAD4 exome AF: 0.0000527 AC: 77AN: 1461726Hom.: 0 Cov.: 30 AF XY: 0.0000523 AC XY: 38AN XY: 727166
GnomAD4 genome AF: 0.0000461 AC: 7AN: 151940Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74224
ClinVar
Submissions by phenotype
Intellectual disability-hypotonia-spasticity-sleep disorder syndrome Uncertain:2
This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2,PP3. -
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not provided Uncertain:1
This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 4377 of the ANK3 protein (p.Ser4377Leu). This variant is present in population databases (rs201169886, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ANK3-related conditions. ClinVar contains an entry for this variant (Variation ID: 930643). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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