dbSNP rs148268550: MLLT10:p.Ser366Asn (chr10-21673395-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001195626.3(MLLT10):c.1097G>A(p.Ser366Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000787 in 1,486,444 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 0.00020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000067 ( 0 hom. )

Consequence

MLLT10
NM_001195626.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.96

Publications

0 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:

ENSG00000304565 (HGNC:):

ENSG00000304565 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21225879).

BS2

High AC in GnomAd4 at 27 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLLT10	NM_001195626.3 link	c.1097G>A	p.Ser366Asn	missense_variant	Exon 11 of 23	ENST00000307729.12	NP_001182555.1	P55197-4Q59EQ6Q6N002
MLLT10	NM_004641.4 link	c.1097G>A	p.Ser366Asn	missense_variant	Exon 11 of 24		NP_004632.1	P55197-1Q59EQ6Q6N002
MLLT10	NM_001324297.2 link	c.362G>A	p.Ser121Asn	missense_variant	Exon 13 of 25		NP_001311226.1
MLLT10	NR_136736.2 link	n.1564G>A		non_coding_transcript_exon_variant	Exon 12 of 26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLLT10	ENST00000307729.12 link	c.1097G>A	p.Ser366Asn	missense_variant	Exon 11 of 23	1	NM_001195626.3	ENSP00000307411.7		P55197-4

Frequencies

GnomAD3 genomes

AF:

0.000193

AC:

AN:

134810

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000279

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

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:

0.000275

Gnomad OTH

AF:

0.000552

GnomAD2 exomes

AF:

0.000103

AC:

AN:

241706

AF XY:

0.0000841

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000218

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000937

Gnomad NFE exome

AF:

0.000118

Gnomad OTH exome

AF:

0.000517

GnomAD4 exome

AF:

0.0000666

AC:

AN:

1351544

Hom.:

Cov.:

AF XY:

0.0000536

AC XY:

AN XY:

671126

show subpopulations

African (AFR)

AF:

0.000135

AC:

AN:

29708

American (AMR)

AF:

0.000231

AC:

AN:

38928

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21522

East Asian (EAS)

AF:

0.00

AC:

AN:

30770

South Asian (SAS)

AF:

0.00

AC:

AN:

83092

European-Finnish (FIN)

AF:

0.0000430

AC:

AN:

46524

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5138

European-Non Finnish (NFE)

AF:

0.0000671

AC:

AN:

1042842

Other (OTH)

AF:

0.0000943

AC:

AN:

53020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000200

AC:

AN:

134900

Hom.:

Cov.:

AF XY:

0.000203

AC XY:

AN XY:

63890

show subpopulations

African (AFR)

AF:

0.0000557

AC:

AN:

35922

American (AMR)

AF:

0.000523

AC:

AN:

11470

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3404

East Asian (EAS)

AF:

0.00

AC:

AN:

4296

South Asian (SAS)

AF:

0.00

AC:

AN:

4140

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7248

Middle Eastern (MID)

AF:

0.00

AC:

AN:

224

European-Non Finnish (NFE)

AF:

0.000275

AC:

AN:

65478

Other (OTH)

AF:

0.000548

AC:

AN:

1826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000133

Hom.:

Bravo

AF:

0.000159

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000123

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 16, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1097G>A (p.S366N) 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 1097, causing the serine (S) at amino acid position 366 to be replaced by an asparagine (N). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.42

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;.;T;T

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

.;D;.;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.21

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M;M;M

PhyloP100

8.0

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.7

.;N;N;N

REVEL

Benign

0.21

Sift

Pathogenic

0.0

.;D;D;D

Sift4G

Benign

0.091

T;T;T;T

Polyphen

0.99

D;.;D;D

Vest4

0.44

MVP

0.51

MPC

0.41

ClinPred

0.12

GERP RS

6.0

PromoterAI

0.0086

Neutral

(source)

Varity_R

0.42

gMVP

0.37

Mutation Taster

=79/21

polymorphism

(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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rs148268550

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