10-21670513-C-T

Variant names:

• chr10-21670513-C-T
• rs981046142
• NM_001195626.3:c.860C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001195626.3(MLLT10):​c.860C>T​(p.Ala287Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,158 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 0.000013 (0 hom., cov: 32)
• Consequence: MLLT10 NM_001195626.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.32

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3109347).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLLT10	NM_001195626.3	c.860C>T	p.Ala287Val	missense_variant	Exon 10 of 23	ENST00000307729.12	NP_001182555.1
MLLT10	NM_004641.4	c.860C>T	p.Ala287Val	missense_variant	Exon 10 of 24		NP_004632.1
MLLT10	NM_001324297.2	c.125C>T	p.Ala42Val	missense_variant	Exon 12 of 25		NP_001311226.1
MLLT10	NR_136736.2	n.1327C>T		non_coding_transcript_exon_variant	Exon 11 of 26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLLT10	ENST00000307729.12	c.860C>T	p.Ala287Val	missense_variant	Exon 10 of 23	1	NM_001195626.3	ENSP00000307411.7

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152158 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74326

Gnomad4 AFR AF: 0.0000483

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: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 15, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.860C>T (p.A287V) alteration is located in exon 9 (coding exon 9) of the MLLT10 gene. This alteration results from a C to T substitution at nucleotide position 860, causing the alanine (A) at amino acid position 287 to be replaced by a valine (V). 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	0.52
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;.;T;T;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.98	.;D;.;D;.
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.31	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;M;M;M;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.0	.;N;N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0010	.;D;D;D;D
Sift4G	Benign	0.26	T;T;T;T;D
Polyphen		0.78	P;.;P;P;.
Vest4		0.66
MutPred		0.31		Gain of sheet (P = 0.0036);Gain of sheet (P = 0.0036);Gain of sheet (P = 0.0036);Gain of sheet (P = 0.0036);.;
MVP		0.33
MPC		0.19
ClinPred		0.75	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs981046142; hg19: chr10-21959442; COSMIC: COSV105886412; COSMIC: COSV105886412;