Genetic Variant MLLT10:c.406-10dupT (chr10-21612326-C-CT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001195626.3(MLLT10):c.406-10dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0157 in 1,215,648 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 31)

Exomes 𝑓: 0.018 ( 0 hom. )

Consequence

MLLT10
NM_001195626.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.05

Publications

0 publications found

Variant links:

Genes affected

MLLT10 (HGNC:16063): (MLLT10 histone lysine methyltransferase DOT1L cofactor) This gene encodes a transcription factor and has been identified as a partner gene involved in several chromosomal rearrangements resulting in various leukemias. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2010]

MLLT10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 73 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195626.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MLLT10	NM_001195626.3	MANE Select	c.406-10dupT	intron	N/A	NP_001182555.1	P55197-4
MLLT10	NM_004641.4		c.406-10dupT	intron	N/A	NP_004632.1	P55197-1
MLLT10	NM_001324297.2		c.-466-10dupT	intron	N/A	NP_001311226.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MLLT10	ENST00000307729.12	TSL:1 MANE Select	c.406-10dupT	intron	N/A	ENSP00000307411.7	P55197-4
MLLT10	ENST00000377059.7	TSL:1	c.406-10dupT	intron	N/A	ENSP00000366258.4	P55197-4
MLLT10	ENST00000377072.8	TSL:1	c.406-10dupT	intron	N/A	ENSP00000366272.3	P55197-1

Frequencies

GnomAD3 genomes

AF:

0.000495

AC:

AN:

143394

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00140

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000403

Gnomad SAS

AF:

0.000443

Gnomad FIN

AF:

0.000681

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000308

Gnomad OTH

AF:

0.00155

GnomAD2 exomes

AF:

0.0144

AC:

1600

AN:

111054

AF XY:

0.0142

show subpopulations

Gnomad AFR exome

AF:

0.00971

Gnomad AMR exome

AF:

0.0187

Gnomad ASJ exome

AF:

0.0122

Gnomad EAS exome

AF:

0.0167

Gnomad FIN exome

AF:

0.0174

Gnomad NFE exome

AF:

0.0130

Gnomad OTH exome

AF:

0.0183

GnomAD4 exome

AF:

0.0177

AC:

18971

AN:

1072220

Hom.:

Cov.:

AF XY:

0.0173

AC XY:

9327

AN XY:

539392

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0139

AC:

340

AN:

24380

American (AMR)

AF:

0.0123

AC:

359

AN:

29278

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

247

AN:

20376

East Asian (EAS)

AF:

0.00902

AC:

300

AN:

33258

South Asian (SAS)

AF:

0.0189

AC:

1235

AN:

65344

European-Finnish (FIN)

AF:

0.0107

AC:

428

AN:

40090

Middle Eastern (MID)

AF:

0.00902

AC:

AN:

4436

European-Non Finnish (NFE)

AF:

0.0189

AC:

15292

AN:

809764

Other (OTH)

AF:

0.0161

AC:

730

AN:

45294

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.258

Heterozygous variant carriers

2307

4614

6921

9228

11535

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

662

1324

1986

2648

3310

<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

AF:

0.000509

AC:

AN:

143428

Hom.:

Cov.:

AF XY:

0.000574

AC XY:

AN XY:

69628

show subpopulations

African (AFR)

AF:

0.000507

AC:

AN:

39420

American (AMR)

AF:

0.00140

AC:

AN:

14332

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3358

East Asian (EAS)

AF:

0.000405

AC:

AN:

4944

South Asian (SAS)

AF:

0.000444

AC:

AN:

4500

European-Finnish (FIN)

AF:

0.000681

AC:

AN:

8810

Middle Eastern (MID)

AF:

0.00

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.000308

AC:

AN:

64952

Other (OTH)

AF:

0.00154

AC:

AN:

1944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00733

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.1

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

10-21612326-CTTTTT-CTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over