Variant 2-210024081-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152519.4(KANSL1L):c.2685T>A(p.Asp895Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)

Consequence

KANSL1L
NM_152519.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0860

Variant links:

Genes affected

KANSL1L (HGNC:26310): (KAT8 regulatory NSL complex subunit 1 like) Predicted to enable histone acetyltransferase binding activity. Predicted to be part of NSL complex. [provided by Alliance of Genome Resources, Apr 2022]

KANSL1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.061453372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANSL1L	NM_152519.4 linkuse as main transcript	c.2685T>A	p.Asp895Glu	missense_variant	14/15	ENST00000281772.14	NP_689732.2	A0AUZ9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KANSL1L	ENST00000281772.14 linkuse as main transcript	c.2685T>A	p.Asp895Glu	missense_variant	14/15	5	NM_152519.4	ENSP00000281772.8	A0AUZ9-1
KANSL1L	ENST00000418791.5 linkuse as main transcript	c.2559T>A	p.Asp853Glu	missense_variant	13/14	1		ENSP00000405724.1	A0AUZ9-2
KANSL1L	ENST00000634716.1 linkuse as main transcript	n.*230T>A		non_coding_transcript_exon_variant	6/7	5		ENSP00000489299.1	A0A0U1RR24
KANSL1L	ENST00000634716.1 linkuse as main transcript	n.*230T>A		3_prime_UTR_variant	6/7	5		ENSP00000489299.1	A0A0U1RR24

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 28, 2024

The c.2685T>A (p.D895E) alteration is located in exon 14 (coding exon 13) of the KANSL1L gene. This alteration results from a T to A substitution at nucleotide position 2685, causing the aspartic acid (D) at amino acid position 895 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.99

DANN

Benign

0.72

DEOGEN2

Benign

0.0029

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.56

T;T

M_CAP

Benign

0.0098

MetaRNN

Benign

0.061

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.41

N;N

REVEL

Benign

0.045

Sift

Benign

0.56

T;T

Sift4G

Benign

0.57

T;T

Polyphen

0.42

B;B

Vest4

0.044

MutPred

0.097

Loss of sheet (P = 0.1398);.;

MVP

0.055

MPC

0.062

ClinPred

0.96

GERP RS

-6.2

Varity_R

0.027

gMVP

0.066

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