10-21586325-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001195626.3(MLLT10):c.272C>G(p.Ala91Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: 7.34

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.787

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MLLT10	NM_001195626.3	c.272C>G	p.Ala91Gly	missense_variant	4/23	ENST00000307729.12
MLLT10	NM_004641.4	c.272C>G	p.Ala91Gly	missense_variant	4/24
MLLT10	NM_001324297.2	c.-600C>G		5_prime_UTR_variant	5/25
MLLT10	NR_136736.2	n.739C>G		non_coding_transcript_exon_variant	5/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLLT10	ENST00000307729.12	c.272C>G	p.Ala91Gly	missense_variant	4/23	1	NM_001195626.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 02, 2022

The c.272C>G (p.A91G) alteration is located in exon 3 (coding exon 3) of the MLLT10 gene. This alteration results from a C to G substitution at nucleotide position 272, causing the alanine (A) at amino acid position 91 to be replaced by a glycine (G). 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	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
Cadd	Pathogenic	29
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.65	D;.;D;D
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.026	D
MetaRNN	Pathogenic	0.79	D;D;D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Pathogenic	3.7	H;H;H;H
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.79	T
Sift4G	Uncertain	0.035	D;D;D;D
Polyphen		1.0	D;.;D;D
Vest4		0.79
MutPred		0.48		Gain of ubiquitination at K93 (P = 0.0516);Gain of ubiquitination at K93 (P = 0.0516);Gain of ubiquitination at K93 (P = 0.0516);Gain of ubiquitination at K93 (P = 0.0516);
MVP		0.63
MPC		2.4
ClinPred		0.99	D
GERP RS		4.5
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.1
Varity_R		0.66
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-21875254; COSMIC: COSV56990406;