rs374061571

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM2PP2BP4_ModerateBS2

The NM_170606.3(KMT2C):ā€‹c.5809C>Gā€‹(p.Gln1937Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,892 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. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

KMT2C
NM_170606.3 missense

Scores

2
16

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 4.69
Variant links:
Genes affected
KMT2C (HGNC:13726): (lysine methyltransferase 2C) This gene is a member of the myeloid/lymphoid or mixed-lineage leukemia (MLL) family and encodes a nuclear protein with an AT hook DNA-binding domain, a DHHC-type zinc finger, six PHD-type zinc fingers, a SET domain, a post-SET domain and a RING-type zinc finger. This protein is a member of the ASC-2/NCOA6 complex (ASCOM), which possesses histone methylation activity and is involved in transcriptional coactivation. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), KMT2C. . Gene score misZ 2.1357 (greater than the threshold 3.09). Trascript score misZ 4.2875 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 40, syndromic intellectual disability, Kleefstra syndrome 2.
BP4
Computational evidence support a benign effect (MetaRNN=0.13296628).
BS2
High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KMT2CNM_170606.3 linkuse as main transcriptc.5809C>G p.Gln1937Glu missense_variant 36/59 ENST00000262189.11 NP_733751.2 Q8NEZ4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KMT2CENST00000262189.11 linkuse as main transcriptc.5809C>G p.Gln1937Glu missense_variant 36/591 NM_170606.3 ENSP00000262189.6 Q8NEZ4-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461892
Hom.:
0
Cov.:
33
AF XY:
0.00000550
AC XY:
4
AN XY:
727246
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:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1

ClinVar

Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link

Submissions by phenotype

not specified Other:1
not provided, no classification providedreference populationITMISep 19, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.094
BayesDel_addAF
Benign
-0.065
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
16
DANN
Benign
0.79
DEOGEN2
Benign
0.063
T;T
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.21
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.85
.;T
M_CAP
Benign
0.027
D
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-0.65
T
MutationAssessor
Uncertain
2.5
M;M
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.87
N;N
REVEL
Benign
0.17
Sift
Benign
0.057
T;T
Polyphen
0.19
B;B
Vest4
0.35
MVP
0.42
MPC
0.11
ClinPred
0.19
T
GERP RS
5.1
Varity_R
0.087
gMVP
0.28

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.

Other links and lift over

dbSNP: rs374061571; hg19: chr7-151879136; API