Variant 17-46171471-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015443.4(KANSL1):c.673A>G(p.Asn225Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,568,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict 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: 2.62

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001316905).

BP6

Variant 17-46171471-T-C is Benign according to our data. Variant chr17-46171471-T-C is described in ClinVar as [Benign]. Clinvar id is 323790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-46171471-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANSL1	NM_015443.4 link	c.673A>G	p.Asn225Asp	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 link	c.673A>G	p.Asn225Asp	missense_variant	2/15	1	NM_015443.4	ENSP00000387393.3		Q7Z3B3-1

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17185

AN:

149994

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0345

Gnomad AMI

AF:

0.248

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0529

Gnomad FIN

AF:

0.0564

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.174

Gnomad OTH

AF:

0.149

GnomAD3 exomes

AF:

0.113

AC:

27969

AN:

246450

Hom.:

AF XY:

0.115

AC XY:

15271

AN XY:

133046

show subpopulations

Gnomad AFR exome

AF:

0.0318

Gnomad AMR exome

AF:

0.0983

Gnomad ASJ exome

AF:

0.177

Gnomad EAS exome

AF:

0.000598

Gnomad SAS exome

AF:

0.0506

Gnomad FIN exome

AF:

0.0583

Gnomad NFE exome

AF:

0.170

Gnomad OTH exome

AF:

0.139

GnomAD4 exome

AF:

0.152

AC:

215603

AN:

1418612

Hom.:

Cov.:

AF XY:

0.150

AC XY:

105724

AN XY:

706244

show subpopulations

Gnomad4 AFR exome

AF:

0.0296

Gnomad4 AMR exome

AF:

0.104

Gnomad4 ASJ exome

AF:

0.188

Gnomad4 EAS exome

AF:

0.000831

Gnomad4 SAS exome

AF:

0.0550

Gnomad4 FIN exome

AF:

0.0650

Gnomad4 NFE exome

AF:

0.175

Gnomad4 OTH exome

AF:

0.141

GnomAD4 genome

AF:

0.114

AC:

17172

AN:

150112

Hom.:

Cov.:

AF XY:

0.107

AC XY:

7852

AN XY:

73394

show subpopulations

Gnomad4 AFR

AF:

0.0344

Gnomad4 AMR

AF:

0.143

Gnomad4 ASJ

AF:

0.181

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0527

Gnomad4 FIN

AF:

0.0564

Gnomad4 NFE

AF:

0.174

Gnomad4 OTH

AF:

0.147

Alfa

AF:

0.161

Hom.:

ESP6500AA

AF:

0.0379

AC:

167

ESP6500EA

AF:

0.182

AC:

1565

ExAC

AF:

0.120

AC:

14625

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

Benign

0.13

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.071

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.90

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

MetaRNN

Benign

0.0013

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

MetaSVM

Benign

-0.71

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.33

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

REVEL

Benign

0.058

Sift

Benign

0.14

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

Sift4G

Benign

0.64

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

Vest4

0.20

MPC

0.020

ClinPred

0.0047

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.13

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