rs772236084
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_015443.4(KANSL1):c.889C>T(p.Arg297Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000164 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_015443.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KANSL1 | NM_015443.4 | c.889C>T | p.Arg297Cys | missense_variant | Exon 2 of 15 | ENST00000432791.7 | NP_056258.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 152072Hom.: 0 Cov.: 35 FAILED QC
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251432Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135890
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461894Hom.: 0 Cov.: 33 AF XY: 0.0000138 AC XY: 10AN XY: 727248
GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152072Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 74274
ClinVar
Submissions by phenotype
Koolen-de Vries syndrome Uncertain:2
Due to the possible presence of a polymorphic segmental duplication, the location of the variant could not be unambiguously resolved. Variants with ambiguous mapping are still reported relative to the KANSL1 transcript. This sequence change replaces arginine with cysteine at codon 297 of the KANSL1 protein (p.Arg297Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. The frequency data for this variant in the population databases (ExAC) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. This variant has not been reported in the literature in individuals with KANSL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 517800). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Until the location of this sequence change can be resolved, the clinical significance of this variant remains uncertain. It has been classified as a Variant of Uncertain Significance. -
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Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at