10-21673392-G-T

Variant summary

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

The NM_001195626.3(MLLT10):c.1094G>T(p.Gly365Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: MLLT10 NM_001195626.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.03

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=0.4149575).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MLLT10	NM_001195626.3	c.1094G>T	p.Gly365Val	missense_variant	11/23	ENST00000307729.12
MLLT10	NM_004641.4	c.1094G>T	p.Gly365Val	missense_variant	11/24
MLLT10	NM_001324297.2	c.359G>T	p.Gly120Val	missense_variant	13/25
MLLT10	NR_136736.2	n.1561G>T		non_coding_transcript_exon_variant	12/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLLT10	ENST00000307729.12	c.1094G>T	p.Gly365Val	missense_variant	11/23	1	NM_001195626.3	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 30

Alfa AF: 0.0000331 Hom.: 0

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.1094G>T (p.G365V) alteration is located in exon 10 (coding exon 10) of the MLLT10 gene. This alteration results from a G to T substitution at nucleotide position 1094, causing the glycine (G) at amino acid position 365 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	Benign	0.12
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
Cadd	Pathogenic	29
Dann	Uncertain	0.99
DEOGEN2	Benign	0.13	T;.;T;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.41	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;M;M;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.69	T
Sift4G	Benign	0.46	T;T;T;T
Polyphen		0.99	D;.;D;D
Vest4		0.60
MVP		0.36
MPC		0.43
ClinPred		0.64	D
GERP RS		6.1
Varity_R		0.14
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs1290586719; hg19: chr10-21962321;