10-21612326-CTTTTT-CTTTT

Variant names:

• chr10-21612326-CT-C
• rs369797804
• NM_001195626.3:c.406-10delT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001195626.3(MLLT10):​c.406-10delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0341 in 142,704 control chromosomes in the GnomAD database, including 219 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.034 (219 hom., cov: 31)
  • Exomes 𝑓: 0.28 (49 hom.)
  • Failed GnomAD Quality Control
• Consequence: MLLT10 NM_001195626.3 intron
• Clinical Significance: Not reported in ClinVar
• 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

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.406-10delT		intron	N/A	NP_001182555.1	P55197-4
	MLLT10	NM_004641.4		c.406-10delT		intron	N/A	NP_004632.1	P55197-1
	MLLT10	NM_001324297.2		c.-466-10delT		intron	N/A	NP_001311226.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLLT10	ENST00000307729.12	TSL:1 MANE Select	c.406-10delT		intron	N/A	ENSP00000307411.7	P55197-4
	MLLT10	ENST00000377059.7	TSL:1	c.406-10delT		intron	N/A	ENSP00000366258.4	P55197-4
	MLLT10	ENST00000377072.8	TSL:1	c.406-10delT		intron	N/A	ENSP00000366272.3	P55197-1

Frequencies

GnomAD3 genomes AF: 0.0340 AC: 4846 AN: 142674 Hom.: 215 Cov.: 31

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0166

Gnomad ASJ AF: 0.00210

Gnomad EAS AF: 0.00182

Gnomad SAS AF: 0.00155

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.0101

Gnomad NFE AF: 0.00327

Gnomad OTH AF: 0.0275

GnomAD2 exomes AF: 0.438 AC: 48621 AN: 111054 AF XY: 0.444

Gnomad AFR exome AF: 0.450

Gnomad AMR exome AF: 0.446

Gnomad ASJ exome AF: 0.453

Gnomad EAS exome AF: 0.443

Gnomad FIN exome AF: 0.410

Gnomad NFE exome AF: 0.431

Gnomad OTH exome AF: 0.434

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.280 AC: 251994 AN: 901102 Hom.: 49 Cov.: 0 AF XY: 0.285 AC XY: 128737 AN XY: 451174

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

African (AFR) AF: 0.345 AC: 7197 AN: 20844

American (AMR) AF: 0.334 AC: 8056 AN: 24122

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 5433 AN: 15870

East Asian (EAS) AF: 0.350 AC: 8105 AN: 23136

South Asian (SAS) AF: 0.318 AC: 18137 AN: 57046

European-Finnish (FIN) AF: 0.322 AC: 9764 AN: 30312

Middle Eastern (MID) AF: 0.215 AC: 785 AN: 3644

European-Non Finnish (NFE) AF: 0.266 AC: 183552 AN: 689352

Other (OTH) AF: 0.298 AC: 10965 AN: 36776

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0341 AC: 4870 AN: 142704 Hom.: 219 Cov.: 31 AF XY: 0.0336 AC XY: 2323 AN XY: 69218

African (AFR) AF: 0.106 AC: 4186 AN: 39342

American (AMR) AF: 0.0166 AC: 237 AN: 14256

Ashkenazi Jewish (ASJ) AF: 0.00210 AC: 7 AN: 3336

East Asian (EAS) AF: 0.00182 AC: 9 AN: 4942

South Asian (SAS) AF: 0.00178 AC: 8 AN: 4496

European-Finnish (FIN) AF: 0.0179 AC: 155 AN: 8650

Middle Eastern (MID) AF: 0.0109 AC: 3 AN: 274

European-Non Finnish (NFE) AF: 0.00327 AC: 211 AN: 64578

Other (OTH) AF: 0.0279 AC: 54 AN: 1938

Alfa AF: 0.0959 Hom.: 11

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1
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: rs369797804; hg19: chr10-21901255; COSMIC: COSV56994181;