chr17-46170987-C-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_015443.4(KANSL1):c.1157G>T(p.Ser386Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,614,048 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
Genome browser will be placed here
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.1157G>T | p.Ser386Ile | missense_variant | Exon 2 of 15 | ENST00000432791.7 | NP_056258.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152238Hom.: 0 Cov.: 35
GnomAD4 exome AF: 0.000110 AC: 161AN: 1461810Hom.: 0 Cov.: 30 AF XY: 0.000114 AC XY: 83AN XY: 727210
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152238Hom.: 0 Cov.: 35 AF XY: 0.0000807 AC XY: 6AN XY: 74372
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
This variant is associated with the following publications: (PMID: 22544363) -
- -
Koolen-de Vries syndrome Uncertain:1
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 serine with isoleucine at codon 386 of the KANSL1 or 17q21.31 segmental duplication protein (p.Ser386Ile). The serine residue is highly conserved and there is a large physicochemical difference between serine and isoleucine. 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: 536295). 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at