10-21673498-T-A

Variant names:

• chr10-21673498-T-A
• rs201326052
• NM_001195626.3:c.1200T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001195626.3(MLLT10):​c.1200T>A​(p.His400Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H400H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MLLT10 NM_001195626.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07
• 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]

ENSG00000304565 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16688743).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195626.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLLT10	NM_001195626.3	MANE Select	c.1200T>A	p.His400Gln	missense	Exon 11 of 23	NP_001182555.1	P55197-4
	MLLT10	NM_004641.4		c.1200T>A	p.His400Gln	missense	Exon 11 of 24	NP_004632.1	P55197-1
	MLLT10	NM_001324297.2		c.465T>A	p.His155Gln	missense	Exon 13 of 25	NP_001311226.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLLT10	ENST00000307729.12	TSL:1 MANE Select	c.1200T>A	p.His400Gln	missense	Exon 11 of 23	ENSP00000307411.7	P55197-4
	MLLT10	ENST00000377059.7	TSL:1	c.1200T>A	p.His400Gln	missense	Exon 10 of 22	ENSP00000366258.4	P55197-4
	MLLT10	ENST00000377072.8	TSL:1	c.1200T>A	p.His400Gln	missense	Exon 11 of 24	ENSP00000366272.3	P55197-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461846 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 727222

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.089	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.1
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.083
Sift	Benign	0.41	T
Sift4G	Benign	0.31	T
Polyphen		0.87	P
Vest4		0.32
MutPred		0.12		Gain of relative solvent accessibility (P = 0.1066)
MVP		0.53
MPC		0.073
ClinPred		0.47	T
GERP RS		4.8
PromoterAI		0.025	Neutral
Varity_R		0.079
gMVP		0.31
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs201326052; hg19: chr10-21962427;