7-152181399-G-C

Variant names:

• chr7-152181399-G-C
• rs587778496
• NM_170606.3:c.6461C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_170606.3(KMT2C):​c.6461C>G​(p.Ser2154Cys) 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. 12/21 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)
• Consequence: KMT2C NM_170606.3 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 2.46

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]

ACMG classification

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=0.2294899).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT2C	NM_170606.3	c.6461C>G	p.Ser2154Cys	missense_variant	Exon 36 of 59	ENST00000262189.11	NP_733751.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KMT2C	ENST00000262189.11	c.6461C>G	p.Ser2154Cys	missense_variant	Exon 36 of 59	1	NM_170606.3	ENSP00000262189.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.10	T;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	.;D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Uncertain	0.21	D
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.27
Sift	Benign	0.18	T;T
Polyphen		0.98	D;D
Vest4		0.33
MutPred		0.15		Loss of phosphorylation at S2154 (P = 0.0107);Loss of phosphorylation at S2154 (P = 0.0107);
MVP		0.43
MPC		0.36
ClinPred		0.54	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.32

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

Other links and lift over

dbSNP: rs587778496; hg19: chr7-151878484;