Variant 2-210024087-G-C 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.2679C>G(p.Asn893Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,480 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

KANSL1L
NM_152519.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0880

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:

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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=0.042795092).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANSL1L	NM_152519.4 linkuse as main transcript	c.2679C>G	p.Asn893Lys	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.2679C>G	p.Asn893Lys	missense_variant	14/15	5	NM_152519.4	ENSP00000281772.8	A0AUZ9-1
KANSL1L	ENST00000418791.5 linkuse as main transcript	c.2553C>G	p.Asn851Lys	missense_variant	13/14	1		ENSP00000405724.1	A0AUZ9-2
KANSL1L	ENST00000634716.1 linkuse as main transcript	n.*224C>G		non_coding_transcript_exon_variant	6/7	5		ENSP00000489299.1	A0A0U1RR24
KANSL1L	ENST00000634716.1 linkuse as main transcript	n.*224C>G		3_prime_UTR_variant	6/7	5		ENSP00000489299.1	A0A0U1RR24

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455480

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724102

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:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 26, 2024

The c.2679C>G (p.N893K) alteration is located in exon 14 (coding exon 13) of the KANSL1L gene. This alteration results from a C to G substitution at nucleotide position 2679, causing the asparagine (N) at amino acid position 893 to be replaced by a lysine (K). 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

0.11

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

6.2

DANN

Benign

0.58

DEOGEN2

Benign

0.0028

T;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.65

T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.043

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.37

N;N

REVEL

Benign

0.041

Sift

Benign

0.81

T;T

Sift4G

Benign

0.31

T;T

Polyphen

0.082

B;B

Vest4

0.085

MutPred

0.23

Gain of ubiquitination at N893 (P = 0.0075);.;

MVP

0.14

MPC

0.085

ClinPred

0.068

GERP RS

1.1

Varity_R

0.070

gMVP

0.090

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over