10-21612326-CTT-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001195626.3(MLLT10):c.406-11_406-10del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0063 in 1,194,506 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0071 (0 hom.)
• Consequence: MLLT10 NM_001195626.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.05

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 10-21612326-CTT-C is Benign according to our data. Variant chr10-21612326-CTT-C is described in ClinVar as [Benign]. Clinvar id is 3050487.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 28 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MLLT10	NM_001195626.3	c.406-11_406-10del		intron_variant		ENST00000307729.12
MLLT10	NM_001324297.2	c.-466-11_-466-10del		intron_variant
MLLT10	NM_004641.4	c.406-11_406-10del		intron_variant
MLLT10	NR_136736.2	n.873-11_873-10del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLLT10	ENST00000307729.12	c.406-11_406-10del		intron_variant		1	NM_001195626.3	P1

Frequencies

GnomAD3 genomes AF: 0.000195 AC: 28 AN: 143226 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000254

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000350

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000915

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000770

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00714 AC: 7502 AN: 1051280 Hom.: 0 AF XY: 0.00735 AC XY: 3885 AN XY: 528306

Gnomad4 AFR exome AF: 0.00789

Gnomad4 AMR exome AF: 0.00991

Gnomad4 ASJ exome AF: 0.00751

Gnomad4 EAS exome AF: 0.00360

Gnomad4 SAS exome AF: 0.0108

Gnomad4 FIN exome AF: 0.00669

Gnomad4 NFE exome AF: 0.00692

Gnomad4 OTH exome AF: 0.00669

GnomAD4 genome AF: 0.000195 AC: 28 AN: 143226 Hom.: 0 Cov.: 30 AF XY: 0.000173 AC XY: 12 AN XY: 69472

Gnomad4 AFR AF: 0.000254

Gnomad4 AMR AF: 0.000350

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000915

Gnomad4 NFE AF: 0.0000770

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MLLT10-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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: rs369797804; hg19: chr10-21901255;