Variant 2-96604271-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000431828.6(KANSL3):c.2128T>G(p.Ser710Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00815 in 1,609,264 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0064 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0083 ( 96 hom. )

Consequence

KANSL3
ENST00000431828.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.27

Variant links:

Genes affected

KANSL3 (HGNC:25473): (KAT8 regulatory NSL complex subunit 3) Involved in histone H4-K16 acetylation; histone H4-K5 acetylation; and histone H4-K8 acetylation. Located in nucleoplasm. Part of histone acetyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

KANSL3 links:

KANSL3 (HGNC:):

KANSL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054763258).

BP6

Variant 2-96604271-A-C is Benign according to our data. Variant chr2-96604271-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2651146.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANSL3	NM_001115016.3 linkuse as main transcript	c.2128T>G	p.Ser710Ala	missense_variant	17/21	ENST00000431828.6	NP_001108488.1	Q9P2N6-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANSL3	ENST00000431828.6 linkuse as main transcript	c.2128T>G	p.Ser710Ala	missense_variant	17/21	1	NM_001115016.3	ENSP00000396749.1		Q9P2N6-3

Frequencies

GnomAD3 genomes

AF:

0.00645

AC:

980

AN:

151984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00813

Gnomad ASJ

AF:

0.00835

Gnomad EAS

AF:

0.000388

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.00812

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00945

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00725

AC:

1766

AN:

243466

Hom.:

AF XY:

0.00765

AC XY:

1013

AN XY:

132364

show subpopulations

Gnomad AFR exome

AF:

0.000994

Gnomad AMR exome

AF:

0.00641

Gnomad ASJ exome

AF:

0.00510

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00516

Gnomad FIN exome

AF:

0.00911

Gnomad NFE exome

AF:

0.00980

Gnomad OTH exome

AF:

0.00953

GnomAD4 exome

AF:

0.00833

AC:

12131

AN:

1457162

Hom.:

Cov.:

AF XY:

0.00842

AC XY:

6107

AN XY:

724934

show subpopulations

Gnomad4 AFR exome

AF:

0.00157

Gnomad4 AMR exome

AF:

0.00598

Gnomad4 ASJ exome

AF:

0.00575

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00558

Gnomad4 FIN exome

AF:

0.0101

Gnomad4 NFE exome

AF:

0.00906

Gnomad4 OTH exome

AF:

0.00840

GnomAD4 genome

AF:

0.00644

AC:

980

AN:

152102

Hom.:

Cov.:

AF XY:

0.00642

AC XY:

477

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00133

Gnomad4 AMR

AF:

0.00812

Gnomad4 ASJ

AF:

0.00835

Gnomad4 EAS

AF:

0.000389

Gnomad4 SAS

AF:

0.00540

Gnomad4 FIN

AF:

0.00812

Gnomad4 NFE

AF:

0.00946

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00762

Hom.:

Bravo

AF:

0.00627

TwinsUK

AF:

0.00836

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.00257

AC:

ESP6500EA

AF:

0.00916

AC:

ExAC

AF:

0.00742

AC:

897

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0121

EpiControl

AF:

0.0130

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2023

KANSL3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0055

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;N;N;N;N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.87

REVEL

Benign

0.025

Sift

Benign

0.27

Sift4G

Benign

0.23

Polyphen

0.057

Vest4

0.10

MVP

0.37

MPC

0.18

ClinPred

0.0042

GERP RS

4.8

gMVP

0.18

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