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rs147946863

Positions:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_170606.3(KMT2C):​c.11581G>T​(p.Ala3861Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3861T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

KMT2C
NM_170606.3 missense

Scores

6
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.76
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
PP2
?
    PP2 - Missense variant in a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease
Missense variant where missense usually causes diseases, KMT2C
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (MetaRNN=0.20271918).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KMT2CNM_170606.3 linkuse as main transcriptc.11581G>T p.Ala3861Ser missense_variant 44/59 ENST00000262189.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KMT2CENST00000262189.11 linkuse as main transcriptc.11581G>T p.Ala3861Ser missense_variant 44/591 NM_170606.3 P2Q8NEZ4-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Uncertain
0.045
T
BayesDel_noAF
Benign
-0.17
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.21
T;T;.
Eigen
Uncertain
0.22
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Benign
0.70
D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.20
T;T;T
MetaSVM
Benign
-0.54
T
MutationAssessor
Uncertain
2.1
M;M;.
MutationTaster
Benign
0.98
D;D
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-1.8
N;N;N
REVEL
Uncertain
0.29
Sift
Benign
0.11
T;T;T
Polyphen
0.92
P;P;.
Vest4
0.23
MutPred
0.33
Gain of phosphorylation at A3861 (P = 9e-04);Gain of phosphorylation at A3861 (P = 9e-04);.;
MVP
0.49
MPC
0.22
ClinPred
0.67
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.11
gMVP
0.16

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

hg19: chr7-151856037; API