Variant rs953781410 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.1259C>A(p.Pro420His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 1,347,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P420R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

KMT2B
NM_014727.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.23

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:

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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=0.11689165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KMT2B	NM_014727.3 linkuse as main transcript	c.1259C>A	p.Pro420His	missense_variant	3/37	ENST00000420124.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KMT2B	ENST00000420124.4 linkuse as main transcript	c.1259C>A	p.Pro420His	missense_variant	3/37	1	NM_014727.3	P2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000918

AC:

AN:

108898

Hom.:

AF XY:

0.0000179

AC XY:

AN XY:

55842

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000775

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000148

AC:

AN:

1347036

Hom.:

Cov.:

AF XY:

0.00000152

AC XY:

AN XY:

659460

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:

0.0000142

Gnomad4 FIN exome

AF:

0.0000213

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.033

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.35

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.4

REVEL

Benign

0.10

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0050

Polyphen

0.21

Vest4

0.27

MutPred

0.37

Loss of glycosylation at P420 (P = 0.0047);

MVP

0.18

ClinPred

0.13

GERP RS

1.7

Varity_R

0.085

gMVP

0.22

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over