NM_170606.3:c.10444G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_170606.3(KMT2C):c.10444G>A(p.Val3482Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

KMT2C
NM_170606.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 1.71

Publications

1 publications found

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]

KMT2C Gene-Disease associations (from GenCC):

Kleefstra syndrome 2
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Illumina, Ambry Genetics, Broad Center for Mendelian Genomics
syndromic intellectual disability
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

KMT2C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03751874).

BP6

Variant 7-152163133-C-T is Benign according to our data. Variant chr7-152163133-C-T is described in CliVar as Likely_benign. Clinvar id is 134797.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-152163133-C-T is described in CliVar as Likely_benign. Clinvar id is 134797.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-152163133-C-T is described in CliVar as Likely_benign. Clinvar id is 134797.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-152163133-C-T is described in CliVar as Likely_benign. Clinvar id is 134797.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-152163133-C-T is described in CliVar as Likely_benign. Clinvar id is 134797.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-152163133-C-T is described in CliVar as Likely_benign. Clinvar id is 134797.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-152163133-C-T is described in CliVar as Likely_benign. Clinvar id is 134797.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-152163133-C-T is described in CliVar as Likely_benign. Clinvar id is 134797.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-152163133-C-T is described in CliVar as Likely_benign. Clinvar id is 134797.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-152163133-C-T is described in CliVar as Likely_benign. Clinvar id is 134797.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-152163133-C-T is described in CliVar as Likely_benign. Clinvar id is 134797.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-152163133-C-T is described in CliVar as Likely_benign. Clinvar id is 134797.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-152163133-C-T is described in CliVar as Likely_benign. Clinvar id is 134797.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-152163133-C-T is described in CliVar as Likely_benign. Clinvar id is 134797.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-152163133-C-T is described in CliVar as Likely_benign. Clinvar id is 134797.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-152163133-C-T is described in CliVar as Likely_benign. Clinvar id is 134797.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-152163133-C-T is described in CliVar as Likely_benign. Clinvar id is 134797.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-152163133-C-T is described in CliVar as Likely_benign. Clinvar id is 134797.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT2C	NM_170606.3 link	c.10444G>A	p.Val3482Ile	missense_variant	Exon 43 of 59	ENST00000262189.11	NP_733751.2	Q8NEZ4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KMT2C	ENST00000262189.11 link	c.10444G>A	p.Val3482Ile	missense_variant	Exon 43 of 59	1	NM_170606.3	ENSP00000262189.6		Q8NEZ4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251464

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000752

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.000277

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 16, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.061

T;T;.

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.78

.;T;T

M_CAP

Benign

0.051

MetaRNN

Benign

0.038

T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.2

M;M;.

PhyloP100

1.7

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.31

N;N;N

REVEL

Benign

0.068

Sift

Benign

0.23

T;T;T

Sift4G

Benign

0.60

.;.;T

Polyphen

0.0010

B;B;.

Vest4

0.091

MutPred

0.21

Gain of catalytic residue at V3482 (P = 0.1427);Gain of catalytic residue at V3482 (P = 0.1427);.;

MVP

0.34

MPC

0.082

ClinPred

0.051

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.040

gMVP

0.11

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over