Genetic Variant NM_001195626.3:c.195G>A (chr10-21538867-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_001195626.3(MLLT10):c.195G>A(p.Pro65Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,609,888 control chromosomes in the GnomAD database, including 93,421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.35 ( 9870 hom., cov: 32)

Exomes 𝑓: 0.33 ( 83551 hom. )

Consequence

MLLT10
NM_001195626.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.309

Publications

33 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.042).

BP6

Variant 10-21538867-G-A is Benign according to our data. Variant chr10-21538867-G-A is described in ClinVar as [Benign]. Clinvar id is 3055784.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.309 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLLT10	NM_001195626.3 link	c.195G>A	p.Pro65Pro	synonymous_variant	Exon 3 of 23	ENST00000307729.12	NP_001182555.1	P55197-4Q59EQ6Q6N002

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLLT10	ENST00000307729.12 link	c.195G>A	p.Pro65Pro	synonymous_variant	Exon 3 of 23	1	NM_001195626.3	ENSP00000307411.7		P55197-4

Frequencies

GnomAD3 genomes

AF:

0.350

AC:

53130

AN:

151866

Hom.:

9850

Cov.:

show subpopulations

Gnomad AFR

AF:

0.409

Gnomad AMI

AF:

0.551

Gnomad AMR

AF:

0.297

Gnomad ASJ

AF:

0.422

Gnomad EAS

AF:

0.0492

Gnomad SAS

AF:

0.245

Gnomad FIN

AF:

0.330

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.350

Gnomad OTH

AF:

0.401

GnomAD2 exomes

AF:

0.306

AC:

76762

AN:

250928

AF XY:

0.310

show subpopulations

Gnomad AFR exome

AF:

0.399

Gnomad AMR exome

AF:

0.213

Gnomad ASJ exome

AF:

0.422

Gnomad EAS exome

AF:

0.0443

Gnomad FIN exome

AF:

0.327

Gnomad NFE exome

AF:

0.361

Gnomad OTH exome

AF:

0.338

GnomAD4 exome

AF:

0.331

AC:

482322

AN:

1457904

Hom.:

83551

Cov.:

AF XY:

0.330

AC XY:

239173

AN XY:

725412

show subpopulations

African (AFR)

AF:

0.416

AC:

13879

AN:

33386

American (AMR)

AF:

0.228

AC:

10167

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.423

AC:

11026

AN:

26084

East Asian (EAS)

AF:

0.0350

AC:

1388

AN:

39670

South Asian (SAS)

AF:

0.258

AC:

22168

AN:

86028

European-Finnish (FIN)

AF:

0.322

AC:

17156

AN:

53354

Middle Eastern (MID)

AF:

0.471

AC:

2711

AN:

5760

European-Non Finnish (NFE)

AF:

0.346

AC:

383306

AN:

1108726

Other (OTH)

AF:

0.340

AC:

20521

AN:

60270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

14058

28116

42173

56231

70289

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.350

AC:

53201

AN:

151984

Hom.:

9870

Cov.:

AF XY:

0.345

AC XY:

25655

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.410

AC:

16989

AN:

41438

American (AMR)

AF:

0.296

AC:

4523

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.422

AC:

1466

AN:

3470

East Asian (EAS)

AF:

0.0489

AC:

254

AN:

5190

South Asian (SAS)

AF:

0.245

AC:

1185

AN:

4828

European-Finnish (FIN)

AF:

0.330

AC:

3471

AN:

10526

Middle Eastern (MID)

AF:

0.534

AC:

157

AN:

294

European-Non Finnish (NFE)

AF:

0.350

AC:

23804

AN:

67962

Other (OTH)

AF:

0.404

AC:

851

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1741

3482

5223

6964

8705

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.345

Hom.:

7669

Bravo

AF:

0.350

Asia WGS

AF:

0.218

AC:

761

AN:

3478

EpiCase

AF:

0.378

EpiControl

AF:

0.379

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MLLT10-related disorder

Benign:1

Sep 24, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as 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

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.55

PhyloP100

-0.31

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Mutation Taster

=97/3

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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NM_001195626.3:c.195G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over