rs74483926

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_170606.3(KMT2C):c.10979C>T(p.Ser3660Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0444 in 1,614,162 control chromosomes in the GnomAD database, including 2,196 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 158 hom., cov: 32)

Exomes 𝑓: 0.045 ( 2038 hom. )

Consequence

KMT2C
NM_170606.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 1.97

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015626252).

BP6

Variant 7-152162598-G-A is Benign according to our data. Variant chr7-152162598-G-A is described in ClinVar as [Benign]. Clinvar id is 134792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT2C	NM_170606.3 link	c.10979C>T	p.Ser3660Leu	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.10979C>T	p.Ser3660Leu	missense_variant	Exon 43 of 59	1	NM_170606.3	ENSP00000262189.6		Q8NEZ4-1

Frequencies

GnomAD3 genomes

AF:

0.0359

AC:

5462

AN:

152174

Hom.:

159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00866

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.0256

Gnomad ASJ

AF:

0.0233

Gnomad EAS

AF:

0.167

Gnomad SAS

AF:

0.0770

Gnomad FIN

AF:

0.0308

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0429

Gnomad OTH

AF:

0.0344

GnomAD3 exomes

AF:

0.0477

AC:

11984

AN:

251438

Hom.:

463

AF XY:

0.0497

AC XY:

6761

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00689

Gnomad AMR exome

AF:

0.0236

Gnomad ASJ exome

AF:

0.0225

Gnomad EAS exome

AF:

0.173

Gnomad SAS exome

AF:

0.0706

Gnomad FIN exome

AF:

0.0333

Gnomad NFE exome

AF:

0.0400

Gnomad OTH exome

AF:

0.0347

GnomAD4 exome

AF:

0.0453

AC:

66282

AN:

1461870

Hom.:

2038

Cov.:

AF XY:

0.0463

AC XY:

33697

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00556

Gnomad4 AMR exome

AF:

0.0233

Gnomad4 ASJ exome

AF:

0.0224

Gnomad4 EAS exome

AF:

0.172

Gnomad4 SAS exome

AF:

0.0697

Gnomad4 FIN exome

AF:

0.0305

Gnomad4 NFE exome

AF:

0.0424

Gnomad4 OTH exome

AF:

0.0447

GnomAD4 genome

AF:

0.0359

AC:

5462

AN:

152292

Hom.:

158

Cov.:

AF XY:

0.0370

AC XY:

2757

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00864

Gnomad4 AMR

AF:

0.0256

Gnomad4 ASJ

AF:

0.0233

Gnomad4 EAS

AF:

0.167

Gnomad4 SAS

AF:

0.0766

Gnomad4 FIN

AF:

0.0308

Gnomad4 NFE

AF:

0.0430

Gnomad4 OTH

AF:

0.0364

Alfa

AF:

0.0442

Hom.:

359

Bravo

AF:

0.0352

TwinsUK

AF:

0.0418

AC:

155

ALSPAC

AF:

0.0467

AC:

180

ESP6500AA

AF:

0.00908

AC:

ESP6500EA

AF:

0.0383

AC:

329

ExAC

AF:

0.0477

AC:

5788

Asia WGS

AF:

0.0960

AC:

333

AN:

3478

EpiCase

AF:

0.0413

EpiControl

AF:

0.0374

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 30, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24965397) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: 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

0.063

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.27

CADD

Benign

3.8

DANN

Benign

0.35

DEOGEN2

Benign

0.12

T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.68

.;T;T

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N;.

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.26

Sift

Benign

0.36

T;T;T

Sift4G

Benign

0.78

.;.;T

Polyphen

0.0020

B;B;.

Vest4

0.067

MPC

0.070

ClinPred

0.014

GERP RS

1.7

Varity_R

0.060

gMVP

0.14

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over