rs17662853
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_015443.4(KANSL1):c.662C>T(p.Thr221Ile) variant causes a missense change. The variant allele was found at a frequency of 0.151 in 1,608,748 control chromosomes in the GnomAD database, including 20,799 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.11 ( 1230 hom., cov: 35)
Exomes 𝑓: 0.16 ( 19569 hom. )
Consequence
KANSL1
NM_015443.4 missense
NM_015443.4 missense
Scores
3
12
Clinical Significance
Conservation
PhyloP100: 4.54
Genes affected
KANSL1 (HGNC:24565): (KAT8 regulatory NSL complex subunit 1) This gene encodes a nuclear protein that is a subunit of two protein complexes involved with histone acetylation, the MLL1 complex and the NSL1 complex. The encoded protein has been implicated in a variety of cellular processes including enhancer regulation, cell proliferation, and mitosis. Mutations in this gene are associated with Koolen-de Vries Syndrome. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=9.5272064E-4).
BP6
?
Variant 17-46171482-G-A is Benign according to our data. Variant chr17-46171482-G-A is described in ClinVar as [Benign]. Clinvar id is 323791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-46171482-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KANSL1 | NM_015443.4 | c.662C>T | p.Thr221Ile | missense_variant | 2/15 | ENST00000432791.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KANSL1 | ENST00000432791.7 | c.662C>T | p.Thr221Ile | missense_variant | 2/15 | 1 | NM_015443.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.107 AC: 16280AN: 151682Hom.: 1230 Cov.: 35
GnomAD3 genomes
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16280
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GnomAD3 exomes AF: 0.117 AC: 29267AN: 250096Hom.: 2337 AF XY: 0.119 AC XY: 16144AN XY: 135118
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GnomAD4 exome AF: 0.155 AC: 226190AN: 1456948Hom.: 19569 Cov.: 50 AF XY: 0.153 AC XY: 110776AN XY: 724644
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GnomAD4 genome ? AF: 0.107 AC: 16277AN: 151800Hom.: 1230 Cov.: 35 AF XY: 0.108 AC XY: 8041AN XY: 74194
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651
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662
ESP6500AA
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142
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1314
ExAC
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14919
Asia WGS
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Koolen-de Vries syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
P;P;P;P;P;P
PrimateAI
Benign
T
PROVEAN
Benign
N;.;.;.;.;N;.;.;.
REVEL
Benign
Sift
Uncertain
D;.;.;.;.;D;.;.;.
Sift4G
Benign
T;T;T;.;T;T;.;.;.
Vest4
MPC
0.099
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at