rs11012732

Variant names:

• chr10-21541175-A-G
• rs11012732
• NM_001195626.3:c.240+2263A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001195626.3(MLLT10):​c.240+2263A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 151,984 control chromosomes in the GnomAD database, including 7,549 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (7546 hom., cov: 31)
  • Exomes 𝑓: 0.39 (3 hom.)
• Consequence: MLLT10 NM_001195626.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.327
• Publications: 51 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLLT10	NM_001195626.3	c.240+2263A>G		intron_variant	Intron 3 of 22	ENST00000307729.12	NP_001182555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLLT10	ENST00000307729.12	c.240+2263A>G		intron_variant	Intron 3 of 22	1	NM_001195626.3	ENSP00000307411.7

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46465 AN: 151822 Hom.: 7533 Cov.: 31

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.0122

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.345

GnomAD4 exome AF: 0.386 AC: 17 AN: 44 Hom.: 3 AF XY: 0.294 AC XY: 10 AN XY: 34

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.425 AC: 17 AN: 40

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.306 AC: 46520 AN: 151940 Hom.: 7546 Cov.: 31 AF XY: 0.302 AC XY: 22448 AN XY: 74256

African (AFR) AF: 0.296 AC: 12261 AN: 41434

American (AMR) AF: 0.263 AC: 4013 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1409 AN: 3470

East Asian (EAS) AF: 0.0122 AC: 63 AN: 5170

South Asian (SAS) AF: 0.215 AC: 1036 AN: 4808

European-Finnish (FIN) AF: 0.326 AC: 3435 AN: 10544

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22990 AN: 67922

Other (OTH) AF: 0.348 AC: 736 AN: 2114

Alfa AF: 0.328 Hom.: 24475

Bravo AF: 0.301

Asia WGS AF: 0.167 AC: 583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.39
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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: rs11012732; hg19: chr10-21830104;