Genetic Variant MLLT10:c.1052-11_1052-10delTT (chr10-21673318-CTT-C) – 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.1052-11_1052-10delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 303,722 control chromosomes in the GnomAD database, including 9 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 0)

Exomes 𝑓: 0.16 ( 9 hom. )

Consequence

MLLT10
NM_001195626.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.76

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:

ENSG00000304565 (HGNC:):

ENSG00000304565 links:

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ACMG classification

Classification was made for transcript

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

BS2

High AC in GnomAd4 at 117 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MLLT10	NM_001195626.3 link	c.1052-11_1052-10delTT	intron_variant	Intron 10 of 22	ENST00000307729.12	NP_001182555.1	P55197-4Q59EQ6Q6N002
MLLT10	NM_004641.4 link	c.1052-11_1052-10delTT	intron_variant	Intron 10 of 23		NP_004632.1	P55197-1Q59EQ6Q6N002
MLLT10	NM_001324297.2 link	c.317-11_317-10delTT	intron_variant	Intron 12 of 24		NP_001311226.1
MLLT10	NR_136736.2 link	n.1519-11_1519-10delTT	intron_variant	Intron 11 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLLT10	ENST00000307729.12 link	c.1052-31_1052-30delTT		intron_variant	Intron 10 of 22	1	NM_001195626.3	ENSP00000307411.7		P55197-4

Frequencies

GnomAD3 genomes

AF:

0.00148

AC:

117

AN:

79098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000408

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00299

Gnomad ASJ

AF:

0.000454

Gnomad EAS

AF:

0.000404

Gnomad SAS

AF:

0.00162

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00667

Gnomad NFE

AF:

0.00201

Gnomad OTH

AF:

0.00102

GnomAD4 exome

AF:

0.162

AC:

36494

AN:

224624

Hom.:

AF XY:

0.161

AC XY:

18917

AN XY:

117238

show subpopulations

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

African (AFR)

AF:

0.151

AC:

721

AN:

4790

American (AMR)

AF:

0.132

AC:

1236

AN:

9390

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

831

AN:

4594

East Asian (EAS)

AF:

0.137

AC:

1551

AN:

11336

South Asian (SAS)

AF:

0.0694

AC:

855

AN:

12324

European-Finnish (FIN)

AF:

0.125

AC:

1723

AN:

13772

Middle Eastern (MID)

AF:

0.168

AC:

124

AN:

736

European-Non Finnish (NFE)

AF:

0.176

AC:

27751

AN:

157294

Other (OTH)

AF:

0.164

AC:

1702

AN:

10388

⚠️ 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: 0.380

Heterozygous variant carriers

1811

3622

5433

7244

9055

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00148

AC:

117

AN:

79098

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

AN XY:

35938

show subpopulations

African (AFR)

AF:

0.000408

AC:

AN:

22080

American (AMR)

AF:

0.00299

AC:

AN:

6358

Ashkenazi Jewish (ASJ)

AF:

0.000454

AC:

AN:

2202

East Asian (EAS)

AF:

0.000406

AC:

AN:

2466

South Asian (SAS)

AF:

0.00163

AC:

AN:

1846

European-Finnish (FIN)

AF:

0.000472

AC:

AN:

2120

Middle Eastern (MID)

AF:

0.00725

AC:

AN:

138

European-Non Finnish (NFE)

AF:

0.00201

AC:

AN:

40342

Other (OTH)

AF:

0.00101

AC:

AN:

988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.415

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.8

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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10-21673318-CTTTTTTTTTTTT-CTTTTTTTTTT

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