10-21612326-CTT-C

Variant names:

• chr10-21612326-CTT-C
• rs369797804
• NM_001195626.3:c.406-11_406-10delTT

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_001195626.3(MLLT10):​c.406-11_406-10delTT 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. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0071 (0 hom.)
• Consequence: MLLT10 NM_001195626.3 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.05
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -1 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 no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLLT10	NM_001195626.3	c.406-11_406-10delTT		intron_variant	Intron 5 of 22	ENST00000307729.12	NP_001182555.1
MLLT10	NM_004641.4	c.406-11_406-10delTT		intron_variant	Intron 5 of 23		NP_004632.1
MLLT10	NM_001324297.2	c.-466-11_-466-10delTT		intron_variant	Intron 6 of 24		NP_001311226.1
MLLT10	NR_136736.2	n.873-11_873-10delTT		intron_variant	Intron 6 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLLT10	ENST00000307729.12	c.406-11_406-10delTT		intron_variant	Intron 5 of 22	1	NM_001195626.3	ENSP00000307411.7

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

GnomAD2 exomes AF: 0.0112 AC: 1245 AN: 111054 AF XY: 0.0108

Gnomad AFR exome AF: 0.00983

Gnomad AMR exome AF: 0.0152

Gnomad ASJ exome AF: 0.0108

Gnomad EAS exome AF: 0.0107

Gnomad FIN exome AF: 0.0124

Gnomad NFE exome AF: 0.00973

Gnomad OTH exome AF: 0.0101

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00789 AC: 190 AN: 24068

American (AMR) AF: 0.00991 AC: 280 AN: 28246

Ashkenazi Jewish (ASJ) AF: 0.00751 AC: 150 AN: 19974

East Asian (EAS) AF: 0.00360 AC: 117 AN: 32464

South Asian (SAS) AF: 0.0108 AC: 682 AN: 63128

European-Finnish (FIN) AF: 0.00669 AC: 262 AN: 39164

Middle Eastern (MID) AF: 0.00481 AC: 21 AN: 4370

European-Non Finnish (NFE) AF: 0.00692 AC: 5504 AN: 795628

Other (OTH) AF: 0.00669 AC: 296 AN: 44238

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000254 AC: 10 AN: 39330

American (AMR) AF: 0.000350 AC: 5 AN: 14292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3358

East Asian (EAS) AF: 0.00 AC: 0 AN: 4958

South Asian (SAS) AF: 0.00 AC: 0 AN: 4518

European-Finnish (FIN) AF: 0.000915 AC: 8 AN: 8740

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.0000770 AC: 5 AN: 64908

Other (OTH) AF: 0.00 AC: 0 AN: 1930

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0103 Hom.: 11

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MLLT10-related disorder Benign:1

Jul 15, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1
Mutation Taster		=100/0	polymorphism

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: rs369797804; hg19: chr10-21901255;