17-46171482-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000432791.7(KANSL1):​c.662C>G​(p.Thr221Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T221I) has been classified as Benign.

Frequency

Genomes: not found (cov: 35)

Consequence

KANSL1
ENST00000432791.7 missense

Scores

1
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.54
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08852884).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KANSL1NM_015443.4 linkuse as main transcriptc.662C>G p.Thr221Ser missense_variant 2/15 ENST00000432791.7 NP_056258.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KANSL1ENST00000432791.7 linkuse as main transcriptc.662C>G p.Thr221Ser missense_variant 2/151 NM_015443.4 ENSP00000387393 P4

Frequencies

GnomAD3 genomes
Cov.:
35
GnomAD4 exome
Cov.:
50
GnomAD4 genome
Cov.:
35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
17
DANN
Benign
0.56
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.41
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.54
.;.;.;.;T;T;T;T;T
M_CAP
Benign
0.0092
T
MetaRNN
Benign
0.089
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.99
T
MutationTaster
Benign
1.0
P;P;P;P;P;P
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-0.25
N;.;.;.;.;N;.;.;.
REVEL
Benign
0.066
Sift
Benign
0.37
T;.;.;.;.;T;.;.;.
Sift4G
Benign
0.50
T;T;T;.;T;T;.;.;.
Vest4
0.077
MutPred
0.12
Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP
0.093
MPC
0.019
ClinPred
0.15
T
GERP RS
3.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
gMVP
0.14

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs17662853; hg19: chr17-44248848; API