Genetic Variant MLLT10:c.1052-10dupT (chr10-21673318-C-CT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_001195626.3(MLLT10):c.1052-10dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0097 ( 6 hom., cov: 0)

Exomes 𝑓: 0.019 ( 10 hom. )

Consequence

MLLT10
NM_001195626.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.47

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: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00967 (765/79128) while in subpopulation EAS AF = 0.0195 (48/2466). AF 95% confidence interval is 0.0151. There are 6 homozygotes in GnomAd4. There are 318 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 765 AD gene.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLLT10	ENST00000307729.12 link	c.1052-32_1052-31insT		intron_variant	Intron 10 of 22	1	NM_001195626.3	ENSP00000307411.7		P55197-4

Frequencies

GnomAD3 genomes

AF:

0.00969

AC:

767

AN:

79128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00575

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00787

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.0198

Gnomad SAS

AF:

0.00921

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.0200

Gnomad NFE

AF:

0.0122

Gnomad OTH

AF:

0.00511

GnomAD4 exome

AF:

0.0189

AC:

4310

AN:

227798

Hom.:

Cov.:

AF XY:

0.0186

AC XY:

2211

AN XY:

119006

show subpopulations

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

African (AFR)

AF:

0.0243

AC:

119

AN:

4902

American (AMR)

AF:

0.0133

AC:

128

AN:

9642

Ashkenazi Jewish (ASJ)

AF:

0.0224

AC:

104

AN:

4646

East Asian (EAS)

AF:

0.0292

AC:

340

AN:

11640

South Asian (SAS)

AF:

0.0101

AC:

127

AN:

12522

European-Finnish (FIN)

AF:

0.0124

AC:

173

AN:

13964

Middle Eastern (MID)

AF:

0.0161

AC:

AN:

744

European-Non Finnish (NFE)

AF:

0.0194

AC:

3096

AN:

159240

Other (OTH)

AF:

0.0201

AC:

211

AN:

10498

⚠️ 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: 0.326

Heterozygous variant carriers

383

766

1150

1533

1916

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00967

AC:

765

AN:

79128

Hom.:

Cov.:

AF XY:

0.00884

AC XY:

318

AN XY:

35960

show subpopulations

African (AFR)

AF:

0.00570

AC:

126

AN:

22092

American (AMR)

AF:

0.00786

AC:

AN:

6360

Ashkenazi Jewish (ASJ)

AF:

0.0104

AC:

AN:

2204

East Asian (EAS)

AF:

0.0195

AC:

AN:

2466

South Asian (SAS)

AF:

0.00922

AC:

AN:

1844

European-Finnish (FIN)

AF:

0.000471

AC:

AN:

2122

Middle Eastern (MID)

AF:

0.0217

AC:

AN:

138

European-Non Finnish (NFE)

AF:

0.0122

AC:

492

AN:

40360

Other (OTH)

AF:

0.00508

AC:

AN:

984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

101

134

168

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

-2.5

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-CTTTTTTTTTTTTT

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