Variant 10-21670478-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001195626.3(MLLT10):c.825A>G(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 (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

MLLT10
NM_001195626.3 missense

Scores

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]

MLLT10 links:

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 GnomAd at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MLLT10	NM_001195626.3 linkuse as main transcript	c.825A>G	p.Ile275Met	missense_variant	10/23	ENST00000307729.12
MLLT10	NM_004641.4 linkuse as main transcript	c.825A>G	p.Ile275Met	missense_variant	10/24
MLLT10	NM_001324297.2 linkuse as main transcript	c.90A>G	p.Ile30Met	missense_variant	12/25
MLLT10	NR_136736.2 linkuse as main transcript	n.1292A>G		non_coding_transcript_exon_variant	11/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLLT10	ENST00000307729.12 linkuse as main transcript	c.825A>G	p.Ile275Met	missense_variant	10/23	1	NM_001195626.3	P1	P55197-4

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152186

Hom.:

Cov.:

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:

AN:

251058

Hom.:

AF XY:

0.00

AC XY:

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:

AN:

1461706

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

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:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

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:

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 submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The 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

BayesDel_noAF

Benign

-0.58

Cadd

Benign

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

M_CAP

Benign

0.0046

MetaRNN

Benign

0.021

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.57

N;N;N;N;.

MutationTaster

Benign

0.87

D;D;D;D

PrimateAI

Benign

0.40

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over