Variant rs752029022 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015443.4(KANSL1):c.3272G>A(p.Arg1091Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

KANSL1
NM_015443.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.27

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]

KANSL1 links:

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=0.1699371).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANSL1	NM_015443.4 linkuse as main transcript	c.3272G>A	p.Arg1091Gln	missense_variant	15/15	ENST00000432791.7	NP_056258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANSL1	ENST00000432791.7 linkuse as main transcript	c.3272G>A	p.Arg1091Gln	missense_variant	15/15	1	NM_015443.4	ENSP00000387393	P4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

249134

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461504

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727046

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Koolen-de Vries syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 27, 2017

This sequence change replaces arginine with glutamine at codon 1091 of the KANSL1 protein (p.Arg1091Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with KANSL1-related disease. This variant is present in population databases (rs752029022, ExAC 0.009%). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Pathogenic

1.0

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.91

.;.;.;.;D;D;D

M_CAP

Benign

0.0086

MetaRNN

Benign

0.17

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.86

D;D;D;D;D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.21

N;.;.;.;.;N;.

REVEL

Benign

0.090

Sift

Pathogenic

0.0

D;.;.;.;.;D;.

Sift4G

Pathogenic

0.0

.;D;.;.;T;D;.

Vest4

0.29, 0.26, 0.30

MutPred

0.36

Loss of MoRF binding (P = 0.0177);Loss of MoRF binding (P = 0.0177);.;.;.;Loss of MoRF binding (P = 0.0177);.;

MVP

0.28

MPC

1.3

ClinPred

0.35

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.071

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over