Variant rs765213873 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_015443.4(KANSL1):c.530A>T(p.Asn177Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000421 in 1,425,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N177S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

KANSL1
NM_015443.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.36

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.31812567).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KANSL1	NM_015443.4 linkuse as main transcript	c.530A>T	p.Asn177Ile	missense_variant	2/15	ENST00000432791.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KANSL1	ENST00000432791.7 linkuse as main transcript	c.530A>T	p.Asn177Ile	missense_variant	2/15	1	NM_015443.4	P4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000922

AC:

AN:

216862

Hom.:

AF XY:

0.00000853

AC XY:

AN XY:

117260

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000197

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000421

AC:

AN:

1425230

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

707410

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000547

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.99

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

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

M_CAP

Benign

0.055

MetaRNN

Benign

0.32

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

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.85

D;D;D;D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-2.3

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

REVEL

Benign

0.21

Sift

Pathogenic

0.0

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

Sift4G

Uncertain

0.0020

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

Vest4

0.78

MutPred

0.24

Loss of solvent accessibility (P = 0.0058);Loss of solvent accessibility (P = 0.0058);Loss of solvent accessibility (P = 0.0058);Loss of solvent accessibility (P = 0.0058);Loss of solvent accessibility (P = 0.0058);Loss of solvent accessibility (P = 0.0058);Loss of solvent accessibility (P = 0.0058);Loss of solvent accessibility (P = 0.0058);Loss of solvent accessibility (P = 0.0058);

MVP

0.28

MPC

0.15

ClinPred

0.88

GERP RS

5.0

gMVP

0.55

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over