rs11012732

Positions:

• chr10-21541175-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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/exons	MANE	Protein	UniProt
MLLT10	NM_001195626.3	c.240+2263A>G		intron_variant		ENST00000307729.12	NP_001182555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLLT10	ENST00000307729.12	c.240+2263A>G		intron_variant		1	NM_001195626.3	ENSP00000307411	P1

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

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.425

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

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.0122

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.348

Alfa AF: 0.338 Hom.: 9016

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

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

LitVar

Other links and lift over

dbSNP: rs11012732; hg19: chr10-21830104;