rs587778496

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_170606.3(KMT2C):​c.6461C>T​(p.Ser2154Phe) 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. 13/21 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: 31)

Consequence

KMT2C
NM_170606.3 missense

Scores

6
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.46
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.20614818).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KMT2CNM_170606.3 linkc.6461C>T p.Ser2154Phe 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 linkc.6461C>T p.Ser2154Phe missense_variant 36/591 NM_170606.3 ENSP00000262189.6 Q8NEZ4-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Uncertain
0.020
T
BayesDel_noAF
Benign
-0.21
CADD
Uncertain
24
DANN
Benign
0.91
DEOGEN2
Benign
0.076
T;T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.93
.;D
M_CAP
Benign
0.077
D
MetaRNN
Benign
0.21
T;T
MetaSVM
Uncertain
-0.055
T
MutationAssessor
Benign
1.3
L;L
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-1.6
N;N
REVEL
Benign
0.24
Sift
Benign
0.11
T;T
Polyphen
0.95
P;P
Vest4
0.34
MutPred
0.14
Loss of phosphorylation at S2154 (P = 0.0107);Loss of phosphorylation at S2154 (P = 0.0107);
MVP
0.22
MPC
0.36
ClinPred
0.83
D
GERP RS
5.5
Varity_R
0.20
gMVP
0.31

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: rs587778496; hg19: chr7-151878484; API