2-210025195-C-G

Variant summary

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

The NM_152519.4(KANSL1L):ā€‹c.2473G>Cā€‹(p.Val825Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000244 in 1,595,724 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.000026 ( 0 hom. )

Consequence

KANSL1L
NM_152519.4 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.80
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]

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
KANSL1LNM_152519.4 linkuse as main transcriptc.2473G>C p.Val825Leu missense_variant 13/15 ENST00000281772.14 NP_689732.2 A0AUZ9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KANSL1LENST00000281772.14 linkuse as main transcriptc.2473G>C p.Val825Leu missense_variant 13/155 NM_152519.4 ENSP00000281772.8 A0AUZ9-1
KANSL1LENST00000418791.5 linkuse as main transcriptc.2347G>C p.Val783Leu missense_variant 12/141 ENSP00000405724.1 A0AUZ9-2
KANSL1LENST00000634716.1 linkuse as main transcriptn.*18G>C non_coding_transcript_exon_variant 5/75 ENSP00000489299.1 A0A0U1RR24
KANSL1LENST00000634716.1 linkuse as main transcriptn.*18G>C 3_prime_UTR_variant 5/75 ENSP00000489299.1 A0A0U1RR24

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152184
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000358
AC:
9
AN:
251414
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135878
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000202
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000263
AC:
38
AN:
1443540
Hom.:
0
Cov.:
27
AF XY:
0.0000292
AC XY:
21
AN XY:
719344
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000256
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152184
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsSep 11, 2024The c.2473G>C (p.V825L) alteration is located in exon 13 (coding exon 12) of the KANSL1L gene. This alteration results from a G to C substitution at nucleotide position 2473, causing the valine (V) at amino acid position 825 to be replaced by a leucine (L). 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
0.25
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0081
T;.
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.77
T;T
M_CAP
Benign
0.021
T
MetaRNN
Uncertain
0.44
T;T
MetaSVM
Benign
-0.55
T
MutationAssessor
Uncertain
2.5
M;.
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-1.1
N;N
REVEL
Benign
0.13
Sift
Benign
0.11
T;D
Sift4G
Benign
0.18
T;T
Polyphen
1.0
D;D
Vest4
0.51
MutPred
0.19
Gain of disorder (P = 0.1062);.;
MVP
0.46
MPC
0.079
ClinPred
0.48
T
GERP RS
4.4
Varity_R
0.10
gMVP
0.38

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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.

Other links and lift over

dbSNP: rs776222162; hg19: chr2-210889919; API