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GeneBe

10-21538867-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001195626.3(MLLT10):c.195G>A(p.Pro65=) 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 (★).

Frequency

Genomes: 𝑓 0.35 ( 9870 hom., cov: 32)
Exomes 𝑓: 0.33 ( 83551 hom. )

Consequence

MLLT10
NM_001195626.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.309
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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 criteria_provided_single_submitter, 1 stars. Variant chr10-21538867-G-A is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.309 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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/exons MANE UniProt
MLLT10NM_001195626.3 linkuse as main transcriptc.195G>A p.Pro65= synonymous_variant 3/23 ENST00000307729.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MLLT10ENST00000307729.12 linkuse as main transcriptc.195G>A p.Pro65= synonymous_variant 3/231 NM_001195626.3 P1P55197-4

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.350
AC:
53130
AN:
151866
Hom.:
9850
Cov.:
32
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
GnomAD3 exomes
AF:
0.306
AC:
76762
AN:
250928
Hom.:
13239
AF XY:
0.310
AC XY:
42012
AN XY:
135638
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 SAS exome
AF:
0.255
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.:
31
AF XY:
0.330
AC XY:
239173
AN XY:
725412
show subpopulations
Gnomad4 AFR exome
AF:
0.416
Gnomad4 AMR exome
AF:
0.228
Gnomad4 ASJ exome
AF:
0.423
Gnomad4 EAS exome
AF:
0.0350
Gnomad4 SAS exome
AF:
0.258
Gnomad4 FIN exome
AF:
0.322
Gnomad4 NFE exome
AF:
0.346
Gnomad4 OTH exome
AF:
0.340
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.350
AC:
53201
AN:
151984
Hom.:
9870
Cov.:
32
AF XY:
0.345
AC XY:
25655
AN XY:
74272
show subpopulations
Gnomad4 AFR
AF:
0.410
Gnomad4 AMR
AF:
0.296
Gnomad4 ASJ
AF:
0.422
Gnomad4 EAS
AF:
0.0489
Gnomad4 SAS
AF:
0.245
Gnomad4 FIN
AF:
0.330
Gnomad4 NFE
AF:
0.350
Gnomad4 OTH
AF:
0.404
Alfa
AF:
0.344
Hom.:
5838
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: criteria provided, single submitter
LINK: link

Submissions by phenotype

MLLT10-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesSep 24, 2019This 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
11
Dann
Benign
0.55
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1802669; hg19: chr10-21827796; COSMIC: COSV57005677; API