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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MLLT10	NM_001195626.3 link	c.406-10dupT	intron_variant	Intron 5 of 22	ENST00000307729.12	NP_001182555.1	P55197-4Q59EQ6Q6N002
MLLT10	NM_004641.4 link	c.406-10dupT	intron_variant	Intron 5 of 23		NP_004632.1	P55197-1Q59EQ6Q6N002
MLLT10	NM_001324297.2 link	c.-466-10dupT	intron_variant	Intron 6 of 24		NP_001311226.1
MLLT10	NR_136736.2 link	n.873-10dupT	intron_variant	Intron 6 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLLT10	ENST00000307729.12 link	c.406-10dupT		intron_variant	Intron 5 of 22	1	NM_001195626.3	ENSP00000307411.7		P55197-4

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 = 0.000000), 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

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

Alfa

AF:

0.00733

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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10-21612326-CTTTTT-CTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over