rs34043286

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015443.4(KANSL1):c.2152T>C(p.Ser718Pro) variant causes a missense change. The variant allele was found at a frequency of 0.189 in 1,614,026 control chromosomes in the GnomAD database, including 32,774 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2131 hom., cov: 33)

Exomes 𝑓: 0.19 ( 30643 hom. )

Consequence

KANSL1
NM_015443.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 5.04

Publications

43 publications found

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 Gene-Disease associations (from GenCC):

Koolen-de Vries syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), ClinGen
Koolen-de Vries syndrome due to a point mutation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KANSL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0010493994).

BP6

Variant 17-46039753-A-G is Benign according to our data. Variant chr17-46039753-A-G is described in ClinVar as [Benign]. Clinvar id is 323774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANSL1	NM_015443.4 link	c.2152T>C	p.Ser718Pro	missense_variant	Exon 8 of 15	ENST00000432791.7	NP_056258.1	Q7Z3B3-1A0A024R9Y2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KANSL1	ENST00000432791.7 link	c.2152T>C	p.Ser718Pro	missense_variant	Exon 8 of 15	1	NM_015443.4	ENSP00000387393.3		Q7Z3B3-1

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21811

AN:

152118

Hom.:

2133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0429

Gnomad AMI

AF:

0.277

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0739

Gnomad FIN

AF:

0.0649

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.185

GnomAD2 exomes

AF:

0.145

AC:

36480

AN:

251370

AF XY:

0.149

show subpopulations

Gnomad AFR exome

AF:

0.0398

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.254

Gnomad EAS exome

AF:

0.000653

Gnomad FIN exome

AF:

0.0680

Gnomad NFE exome

AF:

0.214

Gnomad OTH exome

AF:

0.175

GnomAD4 exome

AF:

0.193

AC:

282744

AN:

1461790

Hom.:

30643

Cov.:

AF XY:

0.191

AC XY:

138889

AN XY:

727196

show subpopulations

African (AFR)

AF:

0.0365

AC:

1223

AN:

33478

American (AMR)

AF:

0.125

AC:

5605

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

6699

AN:

26136

East Asian (EAS)

AF:

0.000882

AC:

AN:

39692

South Asian (SAS)

AF:

0.0795

AC:

6857

AN:

86248

European-Finnish (FIN)

AF:

0.0724

AC:

3869

AN:

53420

Middle Eastern (MID)

AF:

0.202

AC:

1163

AN:

5768

European-Non Finnish (NFE)

AF:

0.222

AC:

246609

AN:

1111936

Other (OTH)

AF:

0.177

AC:

10684

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

12359

24718

37078

49437

61796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.143

AC:

21800

AN:

152236

Hom.:

2131

Cov.:

AF XY:

0.134

AC XY:

9979

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0428

AC:

1780

AN:

41548

American (AMR)

AF:

0.176

AC:

2686

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

834

AN:

3470

East Asian (EAS)

AF:

0.00154

AC:

AN:

5184

South Asian (SAS)

AF:

0.0739

AC:

356

AN:

4816

European-Finnish (FIN)

AF:

0.0649

AC:

689

AN:

10612

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.217

AC:

14747

AN:

67998

Other (OTH)

AF:

0.182

AC:

384

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

930

1860

2789

3719

4649

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.190

Hom.:

6635

Bravo

AF:

0.148

TwinsUK

AF:

0.233

AC:

864

ALSPAC

AF:

0.242

AC:

931

ESP6500AA

AF:

0.0458

AC:

202

ESP6500EA

AF:

0.224

AC:

1927

ExAC

AF:

0.144

AC:

17507

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 23222517) -

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Koolen-de Vries syndrome

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.79

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.092

LIST_S2

Benign

0.051

.;.;.;.;T;T;T;T;T

MetaRNN

Benign

0.0010

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

MetaSVM

Benign

-0.97

PhyloP100

5.0

PrimateAI

Benign

0.41

PROVEAN

Benign

0.51

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

REVEL

Benign

0.14

Sift

Benign

1.0

T;.;.;.;.;T;.;.;.

Sift4G

Benign

0.44

T;T;T;.;T;T;.;.;.

Vest4

0.018

MPC

0.58

ClinPred

0.0059

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

gMVP

0.14

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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rs34043286

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over