Variant 19-35718056-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014727.3(KMT2B):c.38C>T(p.Pro13Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000405 in 986,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

KMT2B
NM_014727.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.266

Variant links:

Genes affected

KMT2B (HGNC:15840): (lysine methyltransferase 2B) This gene encodes a protein which contains multiple domains including a CXXC zinc finger, three PHD zinc fingers, two FY-rich domains, and a SET (suppressor of variegation, enhancer of zeste, and trithorax) domain. The SET domain is a conserved C-terminal domain that characterizes proteins of the MLL (mixed-lineage leukemia) family. This gene is ubiquitously expressed in adult tissues. It is also amplified in solid tumor cell lines, and may be involved in human cancer. Two alternatively spliced transcript variants encoding distinct isoforms have been reported for this gene, however, the full length nature of the shorter transcript is not known. [provided by RefSeq, Jul 2008]

KMT2B links:

Genome browser will be placed here

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=0.13873413).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KMT2B	NM_014727.3 link	c.38C>T	p.Pro13Leu	missense_variant	1/37	ENST00000420124.4	NP_055542.1	Q9UMN6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KMT2B	ENST00000420124.4 link	c.38C>T	p.Pro13Leu	missense_variant	1/37	1	NM_014727.3	ENSP00000398837.2	Q9UMN6
KMT2B	ENST00000673918.2 link	c.38C>T	p.Pro13Leu	missense_variant	1/37			ENSP00000501283.1	A0A669KBI7
KMT2B	ENST00000687718.1 link	n.38C>T		non_coding_transcript_exon_variant	1/3			ENSP00000510535.1	A0A8I5KWP7
KMT2B	ENST00000692961.1 link	n.38C>T		non_coding_transcript_exon_variant	1/36			ENSP00000509289.1	A0A8I5KPK0

Frequencies

GnomAD3 genomes

AF:

0.00000682

AC:

AN:

146606

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.000494

GnomAD4 exome

AF:

0.00000357

AC:

AN:

840212

Hom.:

Cov.:

AF XY:

0.00000772

AC XY:

AN XY:

388820

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000261

Gnomad4 OTH exome

AF:

0.0000361

GnomAD4 genome

AF:

0.00000682

AC:

AN:

146606

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000494

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Dystonia 28, childhood-onset

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Department of Human Genetics, Hannover Medical School

Jan 17, 2025

ACMG: PM2_Supporting, BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.027

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.54

M_CAP

Pathogenic

0.95

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.0

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.50

REVEL

Benign

0.23

Sift

Benign

0.68

Sift4G

Benign

0.17

Polyphen

0.0

Vest4

0.15

MutPred

0.20

Gain of catalytic residue at P13 (P = 0.0193);

MVP

0.20

ClinPred

0.022

GERP RS

-0.44

Varity_R

0.064

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