rs7220988

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.3029C>T(p.Pro1010Leu) variant causes a missense change. The variant allele was found at a frequency of 0.388 in 1,613,746 control chromosomes in the GnomAD database, including 126,362 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1010A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.35 ( 9606 hom., cov: 31)

Exomes 𝑓: 0.39 ( 116756 hom. )

Consequence

KANSL1
NM_015443.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 4.16

Publications

55 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=5.3045103E-5).

BP6

Variant 17-46032108-G-A is Benign according to our data. Variant chr17-46032108-G-A is described in ClinVar as Benign. ClinVar VariationId is 323764.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANSL1	NM_015443.4 link	c.3029C>T	p.Pro1010Leu	missense_variant	Exon 14 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.3029C>T	p.Pro1010Leu	missense_variant	Exon 14 of 15	1	NM_015443.4	ENSP00000387393.3		Q7Z3B3-1

Frequencies

GnomAD3 genomes

AF:

0.346

AC:

52500

AN:

151788

Hom.:

9611

Cov.:

show subpopulations

Gnomad AFR

AF:

0.257

Gnomad AMI

AF:

0.200

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.433

Gnomad EAS

AF:

0.113

Gnomad SAS

AF:

0.576

Gnomad FIN

AF:

0.432

Gnomad MID

AF:

0.277

Gnomad NFE

AF:

0.403

Gnomad OTH

AF:

0.327

GnomAD2 exomes

AF:

0.375

AC:

94222

AN:

251322

AF XY:

0.390

show subpopulations

Gnomad AFR exome

AF:

0.252

Gnomad AMR exome

AF:

0.275

Gnomad ASJ exome

AF:

0.415

Gnomad EAS exome

AF:

0.114

Gnomad FIN exome

AF:

0.437

Gnomad NFE exome

AF:

0.396

Gnomad OTH exome

AF:

0.367

GnomAD4 exome

AF:

0.392

AC:

573248

AN:

1461838

Hom.:

116756

Cov.:

AF XY:

0.399

AC XY:

289904

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.253

AC:

8462

AN:

33480

American (AMR)

AF:

0.280

AC:

12516

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.414

AC:

10820

AN:

26136

East Asian (EAS)

AF:

0.106

AC:

4199

AN:

39698

South Asian (SAS)

AF:

0.567

AC:

48897

AN:

86252

European-Finnish (FIN)

AF:

0.436

AC:

23277

AN:

53414

Middle Eastern (MID)

AF:

0.298

AC:

1716

AN:

5768

European-Non Finnish (NFE)

AF:

0.396

AC:

439966

AN:

1111978

Other (OTH)

AF:

0.387

AC:

23395

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

20821

41642

62463

83284

104105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13646

27292

40938

54584

68230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.346

AC:

52510

AN:

151908

Hom.:

9606

Cov.:

AF XY:

0.347

AC XY:

25770

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.257

AC:

10635

AN:

41422

American (AMR)

AF:

0.273

AC:

4169

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.433

AC:

1503

AN:

3472

East Asian (EAS)

AF:

0.113

AC:

581

AN:

5152

South Asian (SAS)

AF:

0.576

AC:

2772

AN:

4812

European-Finnish (FIN)

AF:

0.432

AC:

4551

AN:

10532

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.403

AC:

27354

AN:

67924

Other (OTH)

AF:

0.323

AC:

680

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1728

3456

5183

6911

8639

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

536

1072

1608

2144

2680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.378

Hom.:

51704

Bravo

AF:

0.321

TwinsUK

AF:

0.389

AC:

1442

ALSPAC

AF:

0.392

AC:

1510

ESP6500AA

AF:

0.248

AC:

1093

ESP6500EA

AF:

0.397

AC:

3412

ExAC

AF:

0.377

AC:

45777

Asia WGS

AF:

0.354

AC:

1231

AN:

3478

EpiCase

AF:

0.391

EpiControl

AF:

0.386

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

- -

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: 23909765) -

Koolen-de Vries syndrome

Benign:3

Sep 20, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Syndromic intellectual disability

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

MAPT-Related Spectrum Disorders

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

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

0.051

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.94

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.57

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

MetaRNN

Benign

0.000053

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

MetaSVM

Benign

-0.94

PhyloP100

4.2

PrimateAI

Benign

0.35

PROVEAN

Benign

0.65

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

REVEL

Benign

0.058

Sift

Benign

0.74

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

Sift4G

Benign

0.56

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

Vest4

0.028, 0.041, 0.027

MPC

0.47

ClinPred

0.0099

GERP RS

4.6

gMVP

0.054

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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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