Genetic Variant MLLT10:c.406-10delT (chr10-21612326-CT-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001195626.3(MLLT10):c.406-10delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0341 in 142,704 control chromosomes in the GnomAD database, including 219 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.034 ( 219 hom., cov: 31)

Exomes 𝑓: 0.28 ( 49 hom. )

Failed GnomAD Quality Control

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: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.0340

AC:

4846

AN:

142674

Hom.:

215

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0166

Gnomad ASJ

AF:

0.00210

Gnomad EAS

AF:

0.00182

Gnomad SAS

AF:

0.00155

Gnomad FIN

AF:

0.0179

Gnomad MID

AF:

0.0101

Gnomad NFE

AF:

0.00327

Gnomad OTH

AF:

0.0275

GnomAD2 exomes

AF:

0.438

AC:

48621

AN:

111054

AF XY:

0.444

show subpopulations

Gnomad AFR exome

AF:

0.450

Gnomad AMR exome

AF:

0.446

Gnomad ASJ exome

AF:

0.453

Gnomad EAS exome

AF:

0.443

Gnomad FIN exome

AF:

0.410

Gnomad NFE exome

AF:

0.431

Gnomad OTH exome

AF:

0.434

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.280

AC:

251994

AN:

901102

Hom.:

Cov.:

AF XY:

0.285

AC XY:

128737

AN XY:

451174

show subpopulations

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

African (AFR)

AF:

0.345

AC:

7197

AN:

20844

American (AMR)

AF:

0.334

AC:

8056

AN:

24122

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

5433

AN:

15870

East Asian (EAS)

AF:

0.350

AC:

8105

AN:

23136

South Asian (SAS)

AF:

0.318

AC:

18137

AN:

57046

European-Finnish (FIN)

AF:

0.322

AC:

9764

AN:

30312

Middle Eastern (MID)

AF:

0.215

AC:

785

AN:

3644

European-Non Finnish (NFE)

AF:

0.266

AC:

183552

AN:

689352

Other (OTH)

AF:

0.298

AC:

10965

AN:

36776

⚠️ 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: 0.286

Heterozygous variant carriers

20956

41913

62869

83826

104782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0341

AC:

4870

AN:

142704

Hom.:

219

Cov.:

AF XY:

0.0336

AC XY:

2323

AN XY:

69218

show subpopulations

African (AFR)

AF:

0.106

AC:

4186

AN:

39342

American (AMR)

AF:

0.0166

AC:

237

AN:

14256

Ashkenazi Jewish (ASJ)

AF:

0.00210

AC:

AN:

3336

East Asian (EAS)

AF:

0.00182

AC:

AN:

4942

South Asian (SAS)

AF:

0.00178

AC:

AN:

4496

European-Finnish (FIN)

AF:

0.0179

AC:

155

AN:

8650

Middle Eastern (MID)

AF:

0.0109

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.00327

AC:

211

AN:

64578

Other (OTH)

AF:

0.0279

AC:

AN:

1938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

186

372

559

745

931

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0959

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 (auto)

(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-CTTTT

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