10-21534743-C-G

Variant names:

• chr10-21534743-C-G
• rs199515071
• NM_001195626.3:c.99C>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001195626.3(MLLT10):​c.99C>G​(p.Gly33Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. G33G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: MLLT10 NM_001195626.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.73
• Publications: 1 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=2.73 with no splicing effect.

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.99C>G	p.Gly33Gly	synonymous	Exon 2 of 23	NP_001182555.1	P55197-4
	MLLT10	NM_004641.4		c.99C>G	p.Gly33Gly	synonymous	Exon 2 of 24	NP_004632.1	P55197-1
	MLLT10	NM_001195628.2		c.99C>G	p.Gly33Gly	synonymous	Exon 2 of 4	NP_001182557.1	P55197-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLLT10	ENST00000307729.12	TSL:1 MANE Select	c.99C>G	p.Gly33Gly	synonymous	Exon 2 of 23	ENSP00000307411.7	P55197-4
	MLLT10	ENST00000377059.7	TSL:1	c.99C>G	p.Gly33Gly	synonymous	Exon 1 of 22	ENSP00000366258.4	P55197-4
	MLLT10	ENST00000377072.8	TSL:1	c.99C>G	p.Gly33Gly	synonymous	Exon 2 of 24	ENSP00000366272.3	P55197-1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	16
DANN	Benign	0.93
PhyloP100		2.7
PromoterAI		-0.036	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6

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

dbSNP: rs199515071; hg19: chr10-21823672;