Genetic Variant MLLT11:p.Ser25Leu (chr1-151067298-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_006818.4(MLLT11):c.74C>T(p.Ser25Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000144 in 1,461,862 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 (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

MLLT11
NM_006818.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.80

Publications

0 publications found

Variant links:

Genes affected

MLLT11 (HGNC:16997): (MLLT11 transcription factor 7 cofactor) The gene variously symbolized ALL1, HRX, or MLL located on 11q23 has been demonstrated to be fused with a number of translocation partners in cases of leukemia. t(1;11)(q21;q23) translocations that fused the MLL gene to a gene on chromosomal band 1q21 in 2 infants with acute myelomonocytic leukemia have been demonstrated. The N-terminal portion of the MLL gene is critical for leukemogenesis in translocations involving band 11q23. This gene encodes 90 amino acids. It was found to be highly expressed in the thymus but not in peripheral lymphoid tissues. In contrast to its restricted distribution in normal hematopoietic tissue, this gene was expressed in all leukemic cell lines tested. [provided by RefSeq, Jul 2008]

MLLT11 links:

CDC42SE1 (HGNC:17719): (CDC42 small effector 1) Predicted to enable GTPase inhibitor activity. Predicted to be involved in signal transduction. Located in cell junction. [provided by Alliance of Genome Resources, Apr 2022]

CDC42SE1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2961594).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006818.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLLT11	NM_006818.4	MANE Select	c.74C>T	p.Ser25Leu	missense	Exon 2 of 2	NP_006809.1	Q13015

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MLLT11	ENST00000368921.5	TSL:1 MANE Select	c.74C>T	p.Ser25Leu	missense	Exon 2 of 2	ENSP00000357917.3	Q13015
MLLT11	ENST00000889973.1		c.74C>T	p.Ser25Leu	missense	Exon 3 of 3	ENSP00000560032.1
MLLT11	ENST00000889974.1		c.74C>T	p.Ser25Leu	missense	Exon 3 of 3	ENSP00000560033.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000199

AC:

AN:

251486

AF XY:

0.0000221

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000765

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000928

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000899

AC:

AN:

1111994

Other (OTH)

AF:

0.0000166

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.13

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.82

M_CAP

Benign

0.020

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.33

PhyloP100

4.8

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-5.5

REVEL

Uncertain

0.35

Sift

Uncertain

0.0030

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.24

MutPred

0.24

Loss of disorder (P = 0.0272)

MVP

0.25

MPC

0.52

ClinPred

0.95

GERP RS

5.9

Varity_R

0.74

gMVP

0.31

Mutation Taster

=45/55

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over