Variant rs776741181 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.1616G>C(p.Cys539Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,607,956 control chromosomes in the GnomAD database, with no homozygous occurrence. 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.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

KANSL1
NM_015443.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.97

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=0.20699528).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANSL1	NM_015443.4 linkuse as main transcript	c.1616G>C	p.Cys539Ser	missense_variant	5/15	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.1616G>C	p.Cys539Ser	missense_variant	5/15	1	NM_015443.4	ENSP00000387393	P4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251194

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455804

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724634

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.80

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.044

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.86

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

M_CAP

Benign

0.0080

MetaRNN

Benign

0.21

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

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.81

D;D;D;D;D;D

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.3

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

REVEL

Benign

0.20

Sift

Benign

0.42

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

Sift4G

Benign

0.51

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

Vest4

0.36

MutPred

0.61

Gain of disorder (P = 0.0042);Gain of disorder (P = 0.0042);Gain of disorder (P = 0.0042);Gain of disorder (P = 0.0042);Gain of disorder (P = 0.0042);Gain of disorder (P = 0.0042);Gain of disorder (P = 0.0042);Gain of disorder (P = 0.0042);.;Gain of disorder (P = 0.0042);

MVP

0.33

MPC

0.58

ClinPred

0.10

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.50

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over