Variant 17-46171833-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_015443.4(KANSL1):c.311A>C(p.Lys104Thr) variant causes a missense change. The variant allele was found at a frequency of 0.151 in 1,581,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 0 hom., cov: 35)

Exomes 𝑓: 0.15 ( 0 hom. )

Consequence

KANSL1
NM_015443.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.66

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:

KANSL1 (HGNC:):

KANSL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

PM1

In a modified_residue N6-acetyllysine (size 0) in uniprot entity KANL1_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.0015992224).

BP6

Variant 17-46171833-T-G is Benign according to our data. Variant chr17-46171833-T-G is described in ClinVar as [Benign]. Clinvar id is 323797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-46171833-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANSL1	NM_015443.4 linkuse as main transcript	c.311A>C	p.Lys104Thr	missense_variant	2/15	ENST00000432791.7	NP_056258.1	Q7Z3B3-1A0A024R9Y2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANSL1	ENST00000432791.7 linkuse as main transcript	c.311A>C	p.Lys104Thr	missense_variant	2/15	1	NM_015443.4	ENSP00000387393.3		Q7Z3B3-1

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17236

AN:

150222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0343

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0513

Gnomad FIN

AF:

0.0574

Gnomad MID

AF:

0.172

Gnomad NFE

AF:

0.174

Gnomad OTH

AF:

0.150

GnomAD3 exomes

AF:

0.118

AC:

29429

AN:

249468

Hom.:

AF XY:

0.120

AC XY:

16108

AN XY:

134766

show subpopulations

Gnomad AFR exome

AF:

0.0323

Gnomad AMR exome

AF:

0.102

Gnomad ASJ exome

AF:

0.192

Gnomad EAS exome

AF:

0.000544

Gnomad SAS exome

AF:

0.0572

Gnomad FIN exome

AF:

0.0608

Gnomad NFE exome

AF:

0.174

Gnomad OTH exome

AF:

0.144

GnomAD4 exome

AF:

0.155

AC:

221562

AN:

1430848

Hom.:

Cov.:

AF XY:

0.153

AC XY:

108910

AN XY:

712762

show subpopulations

Gnomad4 AFR exome

AF:

0.0300

Gnomad4 AMR exome

AF:

0.108

Gnomad4 ASJ exome

AF:

0.193

Gnomad4 EAS exome

AF:

0.000781

Gnomad4 SAS exome

AF:

0.0593

Gnomad4 FIN exome

AF:

0.0667

Gnomad4 NFE exome

AF:

0.178

Gnomad4 OTH exome

AF:

0.144

GnomAD4 genome

AF:

0.115

AC:

17221

AN:

150336

Hom.:

Cov.:

AF XY:

0.107

AC XY:

7894

AN XY:

73546

show subpopulations

Gnomad4 AFR

AF:

0.0342

Gnomad4 AMR

AF:

0.142

Gnomad4 ASJ

AF:

0.181

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0509

Gnomad4 FIN

AF:

0.0574

Gnomad4 NFE

AF:

0.174

Gnomad4 OTH

AF:

0.148

Alfa

AF:

0.144

Hom.:

258

ESP6500AA

AF:

0.0384

AC:

169

ESP6500EA

AF:

0.183

AC:

1576

ExAC

AF:

0.120

AC:

14610

Asia WGS

AF:

0.0250

AC:

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Koolen-de Vries syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

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

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

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

MetaRNN

Benign

0.0016

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

MetaSVM

Benign

-1.2

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.6

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

REVEL

Benign

0.27

Sift

Pathogenic

0.0

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

Sift4G

Uncertain

0.021

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

Vest4

0.54

MPC

0.15

ClinPred

0.016

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.48

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