Variant 10-21673526-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001195626.3(MLLT10):c.1228G>A(p.Gly410Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000676 in 1,613,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

MLLT10
NM_001195626.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.14

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.29420692).

BS2

High AC in GnomAd at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MLLT10	NM_001195626.3 linkuse as main transcript	c.1228G>A	p.Gly410Arg	missense_variant	11/23	ENST00000307729.12
MLLT10	NM_004641.4 linkuse as main transcript	c.1228G>A	p.Gly410Arg	missense_variant	11/24
MLLT10	NM_001324297.2 linkuse as main transcript	c.493G>A	p.Gly165Arg	missense_variant	13/25
MLLT10	NR_136736.2 linkuse as main transcript	n.1695G>A		non_coding_transcript_exon_variant	12/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLLT10	ENST00000307729.12 linkuse as main transcript	c.1228G>A	p.Gly410Arg	missense_variant	11/23	1	NM_001195626.3	P1	P55197-4

Frequencies

GnomAD3 genomes

AF:

0.0000922

AC:

AN:

151858

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

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:

0.000758

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000837

AC:

AN:

250902

Hom.:

AF XY:

0.0000885

AC XY:

AN XY:

135594

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.000740

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000650

AC:

AN:

1461602

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000880

Gnomad4 NFE exome

AF:

0.0000387

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000922

AC:

AN:

151858

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74148

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000758

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000125

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000741

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

Mar 07, 2023

The c.1228G>A (p.G410R) alteration is located in exon 10 (coding exon 10) of the MLLT10 gene. This alteration results from a G to A substitution at nucleotide position 1228, causing the glycine (G) at amino acid position 410 to be replaced by an arginine (R). 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

0.20

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.39

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.14

T;.;T;T

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.93

M_CAP

Benign

0.0066

MetaRNN

Benign

0.29

T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.7

L;L;L;L

MutationTaster

Benign

0.97

D;D;D;D

PrimateAI

Uncertain

0.50

Sift4G

Benign

0.56

T;T;T;T

Polyphen

0.79

P;.;P;P

Vest4

0.61

MutPred

0.23

Gain of methylation at G410 (P = 0.0166);Gain of methylation at G410 (P = 0.0166);Gain of methylation at G410 (P = 0.0166);Gain of methylation at G410 (P = 0.0166);

MVP

0.18

MPC

0.20

ClinPred

0.19

GERP RS

5.7

Varity_R

0.11

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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