Variant 2-210025207-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152519.4(KANSL1L):c.2461C>G(p.Leu821Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000193 in 1,396,996 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

KANSL1L
NM_152519.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.62

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANSL1L	NM_152519.4 linkuse as main transcript	c.2461C>G	p.Leu821Val	missense_variant	13/15	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.2461C>G	p.Leu821Val	missense_variant	13/15	5	NM_152519.4	ENSP00000281772.8	A0AUZ9-1
KANSL1L	ENST00000418791.5 linkuse as main transcript	c.2335C>G	p.Leu779Val	missense_variant	12/14	1		ENSP00000405724.1	A0AUZ9-2
KANSL1L	ENST00000634716.1 linkuse as main transcript	n.*6C>G		non_coding_transcript_exon_variant	5/7	5		ENSP00000489299.1	A0A0U1RR24
KANSL1L	ENST00000634716.1 linkuse as main transcript	n.*6C>G		3_prime_UTR_variant	5/7	5		ENSP00000489299.1	A0A0U1RR24

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251364

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135850

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:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000193

AC:

AN:

1396996

Hom.:

Cov.:

AF XY:

0.0000215

AC XY:

AN XY:

699100

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:

0.0000256

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Nov 19, 2022

The c.2461C>G (p.L821V) alteration is located in exon 13 (coding exon 12) of the KANSL1L gene. This alteration results from a C to G substitution at nucleotide position 2461, causing the leucine (L) at amino acid position 821 to be replaced by a valine (V). 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

0.14

BayesDel_addAF

Uncertain

0.074

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.084

T;.

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.031

MetaRNN

Uncertain

0.63

D;D

MetaSVM

Benign

-0.29

MutationAssessor

Uncertain

2.9

M;.

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.25

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.027

D;D

Polyphen

1.0

D;D

Vest4

0.65

MVP

0.66

MPC

0.37

ClinPred

0.94

GERP RS

5.3

Varity_R

0.27

gMVP

0.34

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