10-21670478-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001195626.3(MLLT10):ā€‹c.825A>Gā€‹(p.Ile275Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000046 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000082 ( 0 hom. )

Consequence

MLLT10
NM_001195626.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.57
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.021261394).
BS2
High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MLLT10NM_001195626.3 linkuse as main transcriptc.825A>G p.Ile275Met missense_variant 10/23 ENST00000307729.12 NP_001182555.1
MLLT10NM_004641.4 linkuse as main transcriptc.825A>G p.Ile275Met missense_variant 10/24 NP_004632.1
MLLT10NM_001324297.2 linkuse as main transcriptc.90A>G p.Ile30Met missense_variant 12/25 NP_001311226.1
MLLT10NR_136736.2 linkuse as main transcriptn.1292A>G non_coding_transcript_exon_variant 11/26

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MLLT10ENST00000307729.12 linkuse as main transcriptc.825A>G p.Ile275Met missense_variant 10/231 NM_001195626.3 ENSP00000307411 P1P55197-4

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152186
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
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:
0.0000147
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251058
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135704
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461706
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
727146
show subpopulations
Gnomad4 AFR exome
AF:
0.000239
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152186
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000479
Bravo
AF:
0.0000529
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 28, 2024The c.825A>G (p.I275M) alteration is located in exon 9 (coding exon 9) of the MLLT10 gene. This alteration results from a A to G substitution at nucleotide position 825, causing the isoleucine (I) at amino acid position 275 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.059
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
12
DANN
Benign
0.84
DEOGEN2
Benign
0.092
T;.;T;T;.
Eigen
Benign
-0.56
Eigen_PC
Benign
-0.29
FATHMM_MKL
Benign
0.48
N
LIST_S2
Benign
0.76
.;T;.;T;.
M_CAP
Benign
0.0046
T
MetaRNN
Benign
0.021
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.57
N;N;N;N;.
MutationTaster
Benign
0.87
D;D;D;D
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.39
.;N;N;N;N
REVEL
Benign
0.058
Sift
Benign
0.39
.;T;T;T;D
Sift4G
Benign
0.41
T;T;T;T;T
Polyphen
0.0010
B;.;B;B;.
Vest4
0.23
MutPred
0.20
Loss of glycosylation at S274 (P = 0.075);Loss of glycosylation at S274 (P = 0.075);Loss of glycosylation at S274 (P = 0.075);Loss of glycosylation at S274 (P = 0.075);.;
MVP
0.12
MPC
0.073
ClinPred
0.036
T
GERP RS
3.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.060
gMVP
0.092

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: rs529826847; hg19: chr10-21959407; COSMIC: COSV56999631; COSMIC: COSV56999631; API