chr10-21534740-A-T

Variant names:

• chr10-21534740-A-T
• NM_001195626.3:c.96A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001195626.3(MLLT10):​c.96A>T​(p.Arg32Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MLLT10 NM_001195626.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.38
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLLT10	NM_001195626.3	c.96A>T	p.Arg32Ser	missense_variant	Exon 2 of 23	ENST00000307729.12	NP_001182555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLLT10	ENST00000307729.12	c.96A>T	p.Arg32Ser	missense_variant	Exon 2 of 23	1	NM_001195626.3	ENSP00000307411.7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.96A>T (p.R32S) alteration is located in exon 1 (coding exon 1) of the MLLT10 gene. This alteration results from a A to T substitution at nucleotide position 96, causing the arginine (R) at amino acid position 32 to be replaced by a serine (S). 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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T;.;.;T;.;.;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.070	N
LIST_S2	Pathogenic	0.98	.;D;D;.;.;D;D
M_CAP	Pathogenic	0.84	D
MetaRNN	Uncertain	0.69	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.12	D
MutationAssessor	Benign	0.97	L;L;L;L;L;L;L
PhyloP100		3.4
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-5.2	.;D;D;D;D;.;D
REVEL	Pathogenic	0.71
Sift	Uncertain	0.026	.;D;D;D;T;.;D
Sift4G	Pathogenic	0.0	D;T;D;D;D;D;D
Polyphen		0.95	P;.;.;P;.;.;P
Vest4		0.73
MutPred		0.45		Gain of catalytic residue at R32 (P = 0.0453);Gain of catalytic residue at R32 (P = 0.0453);Gain of catalytic residue at R32 (P = 0.0453);Gain of catalytic residue at R32 (P = 0.0453);Gain of catalytic residue at R32 (P = 0.0453);Gain of catalytic residue at R32 (P = 0.0453);Gain of catalytic residue at R32 (P = 0.0453);
MVP		0.98
MPC		3.3
ClinPred		1.0	D
GERP RS		3.9
PromoterAI		-0.037	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.87
gMVP		0.76
Mutation Taster		=50/50

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

Other links and lift over

hg19: chr10-21823669;