Genetic Variant MLLT10:c.1052-14_1052-10delTTTTT (chr10-21673318-CTTTTT-C) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_001195626.3(MLLT10):c.1052-14_1052-10delTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 307,276 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0015 ( 0 hom. )

Consequence

MLLT10
NM_001195626.3 intron

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.414

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 -1 ACMG points.

BP6

Variant 10-21673318-CTTTTT-C is Benign according to our data. Variant chr10-21673318-CTTTTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 3039949.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MLLT10	NM_001195626.3 link	c.1052-14_1052-10delTTTTT	intron_variant	Intron 10 of 22	ENST00000307729.12	NP_001182555.1	P55197-4Q59EQ6Q6N002
MLLT10	NM_004641.4 link	c.1052-14_1052-10delTTTTT	intron_variant	Intron 10 of 23		NP_004632.1	P55197-1Q59EQ6Q6N002
MLLT10	NM_001324297.2 link	c.317-14_317-10delTTTTT	intron_variant	Intron 12 of 24		NP_001311226.1
MLLT10	NR_136736.2 link	n.1519-14_1519-10delTTTTT	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_1052-27delTTTTT		intron_variant	Intron 10 of 22	1	NM_001195626.3	ENSP00000307411.7		P55197-4

Frequencies

GnomAD3 genomes

AF:

0.0000126

AC:

AN:

79132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000248

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00151

AC:

344

AN:

228144

Hom.:

AF XY:

0.00154

AC XY:

183

AN XY:

119172

show subpopulations

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

African (AFR)

AF:

0.00122

AC:

AN:

4904

American (AMR)

AF:

0.00155

AC:

AN:

9654

Ashkenazi Jewish (ASJ)

AF:

0.00129

AC:

AN:

4646

East Asian (EAS)

AF:

0.00103

AC:

AN:

11668

South Asian (SAS)

AF:

0.000399

AC:

AN:

12534

European-Finnish (FIN)

AF:

0.00100

AC:

AN:

13962

Middle Eastern (MID)

AF:

0.00269

AC:

AN:

744

European-Non Finnish (NFE)

AF:

0.00166

AC:

265

AN:

159514

Other (OTH)

AF:

0.00181

AC:

AN:

10518

⚠️ 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: 0.263

Heterozygous variant carriers

115

153

191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000126

AC:

AN:

79132

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35944

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22074

American (AMR)

AF:

0.00

AC:

AN:

6352

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2204

East Asian (EAS)

AF:

0.00

AC:

AN:

2474

South Asian (SAS)

AF:

0.00

AC:

AN:

1848

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2122

Middle Eastern (MID)

AF:

0.00

AC:

AN:

150

European-Non Finnish (NFE)

AF:

0.0000248

AC:

AN:

40370

Other (OTH)

AF:

0.00

AC:

AN:

980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MLLT10-related disorder

Benign:1

Apr 09, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.41

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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10-21673318-CTTTTT-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over