Variant 7-105110840-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_182931.3(KMT2E):c.4040C>T(p.Thr1347Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,524 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. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1347S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

KMT2E
NM_182931.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.32

Variant links:

Genes affected

KMT2E (HGNC:18541): (lysine methyltransferase 2E (inactive)) This gene is a member of the myeloid/lymphoid or mixed-lineage leukemia (MLL) family and encodes a protein with an N-terminal PHD zinc finger and a central SET domain. Overexpression of the protein inhibits cell cycle progression. Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

KMT2E links:

SRPK2 (HGNC:11306): (SRSF protein kinase 2) Enables ATP binding activity; magnesium ion binding activity; and protein serine/threonine kinase activity. Involved in several processes, including nucleic acid metabolic process; peptidyl-serine phosphorylation; and regulation of viral genome replication. Located in chromatin; cytosol; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

SRPK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.092912585).

BP6

Variant 7-105110840-C-T is Benign according to our data. Variant chr7-105110840-C-T is described in ClinVar as [Benign]. Clinvar id is 2868191.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KMT2E	NM_182931.3 linkuse as main transcript	c.4040C>T	p.Thr1347Ile	missense_variant	26/27	ENST00000311117.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KMT2E	ENST00000311117.8 linkuse as main transcript	c.4040C>T	p.Thr1347Ile	missense_variant	26/27	1	NM_182931.3	P4	Q8IZD2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461524

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727078

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:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.052

T;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.67

.;T

M_CAP

Uncertain

0.093

MetaRNN

Benign

0.093

T;T

MetaSVM

Uncertain

-0.21

MutationAssessor

Benign

0.63

N;N

MutationTaster

Benign

0.99

N;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.18

Sift

Uncertain

0.0010

D;D

Sift4G

Benign

0.17

T;T

Polyphen

0.0

B;B

Vest4

0.24

MutPred

0.13

Loss of glycosylation at T1347 (P = 0.0239);Loss of glycosylation at T1347 (P = 0.0239);

MVP

0.21

MPC

0.056

ClinPred

0.37

GERP RS

3.6

Varity_R

0.14

gMVP

0.10

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over