Variant 19-35718058-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_014727.3(KMT2B):c.40G>A(p.Gly14Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000517 in 986,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G14G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

KMT2B
NM_014727.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.256

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 Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26403773).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KMT2B	NM_014727.3 linkuse as main transcript	c.40G>A	p.Gly14Ser	missense_variant	1/37	ENST00000420124.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
KMT2B	ENST00000420124.4 linkuse as main transcript	c.40G>A	p.Gly14Ser	missense_variant	1/37	1	NM_014727.3	P2
KMT2B	ENST00000673918.2 linkuse as main transcript	c.40G>A	p.Gly14Ser	missense_variant	1/37			A2
KMT2B	ENST00000692961.1 linkuse as main transcript	c.40G>A	p.Gly14Ser	missense_variant, NMD_transcript_variant	1/36
KMT2B	ENST00000687718.1 linkuse as main transcript	c.40G>A	p.Gly14Ser	missense_variant, NMD_transcript_variant	1/3

Frequencies

GnomAD3 genomes

AF:

0.0000273

AC:

AN:

146512

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:

0.0000456

Gnomad OTH

AF:

0.000495

GnomAD4 exome

AF:

0.0000559

AC:

AN:

840276

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

388872

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:

0.0000587

Gnomad4 OTH exome

AF:

0.0000722

GnomAD4 genome

AF:

0.0000273

AC:

AN:

146512

Hom.:

Cov.:

AF XY:

0.0000281

AC XY:

AN XY:

71276

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:

0.0000456

Gnomad4 OTH

AF:

0.000495

Bravo

AF:

0.0000453

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Benign

-0.19

Cadd

Uncertain

Dann

Benign

0.93

DEOGEN2

Benign

0.025

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.51

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.73

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.19

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.015

Polyphen

0.95

Vest4

0.28

MutPred

0.12

Gain of phosphorylation at G14 (P = 0.0028);

MVP

0.45

ClinPred

0.32

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.4

Varity_R

0.078

gMVP

0.11

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