7-152358656-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_170606.3(KMT2C):c.181A>G(p.Thr61Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 1,608,438 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0094 ( 26 hom., cov: 32)

Exomes 𝑓: 0.00097 ( 21 hom. )

Consequence

KMT2C
NM_170606.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: 0.338

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=0.0031529963).

BP6

Variant 7-152358656-T-C is Benign according to our data. Variant chr7-152358656-T-C is described in ClinVar as [Benign]. Clinvar id is 134744.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00942 (1431/151954) while in subpopulation AFR AF= 0.0332 (1376/41432). AF 95% confidence interval is 0.0318. There are 26 homozygotes in gnomad4. There are 694 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1431 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT2C	NM_170606.3 link	c.181A>G	p.Thr61Ala	missense_variant	Exon 2 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.181A>G	p.Thr61Ala	missense_variant	Exon 2 of 59	1	NM_170606.3	ENSP00000262189.6		Q8NEZ4-1

Frequencies

GnomAD3 genomes

AF:

0.00940

AC:

1428

AN:

151836

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0332

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00237

AC:

588

AN:

248582

Hom.:

AF XY:

0.00193

AC XY:

259

AN XY:

134190

show subpopulations

Gnomad AFR exome

AF:

0.0328

Gnomad AMR exome

AF:

0.00134

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000966

AC:

1407

AN:

1456484

Hom.:

Cov.:

AF XY:

0.000857

AC XY:

621

AN XY:

724512

show subpopulations

Gnomad4 AFR exome

AF:

0.0347

Gnomad4 AMR exome

AF:

0.00166

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000361

Gnomad4 OTH exome

AF:

0.00208

GnomAD4 genome

AF:

0.00942

AC:

1431

AN:

151954

Hom.:

Cov.:

AF XY:

0.00934

AC XY:

694

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.0332

Gnomad4 AMR

AF:

0.00236

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00400

Hom.:

Bravo

AF:

0.0106

ESP6500AA

AF:

0.0306

AC:

135

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00287

AC:

348

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 06, 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

0.074

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.27

DEOGEN2

Benign

0.063

T;T;.

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.56

.;T;T

MetaRNN

Benign

0.0032

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

N;N;.

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.97

N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.018

D;D;T

Polyphen

0.0

B;B;.

Vest4

0.17

MVP

0.18

MPC

0.22

ClinPred

0.0050

GERP RS

1.1

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.7

Varity_R

0.046

gMVP

0.20

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