10-21612326-CTTTTT-CTTTTTTT

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001195626.3(MLLT10):​c.406-11_406-10dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000765 in 1,097,940 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000077 (0 hom.)
• 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLLT10	NM_001195626.3	c.406-11_406-10dupTT		intron_variant	Intron 5 of 22	ENST00000307729.12	NP_001182555.1
MLLT10	NM_004641.4	c.406-11_406-10dupTT		intron_variant	Intron 5 of 23		NP_004632.1
MLLT10	NM_001324297.2	c.-466-11_-466-10dupTT		intron_variant	Intron 6 of 24		NP_001311226.1
MLLT10	NR_136736.2	n.873-11_873-10dupTT		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_406-10dupTT		intron_variant	Intron 5 of 22	1	NM_001195626.3	ENSP00000307411.7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000540 AC: 6 AN: 111054 AF XY: 0.0000813

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000226

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000126

Gnomad NFE exome AF: 0.0000384

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000765 AC: 84 AN: 1097940 Hom.: 0 Cov.: 0 AF XY: 0.0000851 AC XY: 47 AN XY: 552170

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

African (AFR) AF: 0.00 AC: 0 AN: 24866

American (AMR) AF: 0.0000671 AC: 2 AN: 29794

Ashkenazi Jewish (ASJ) AF: 0.0000479 AC: 1 AN: 20884

East Asian (EAS) AF: 0.00 AC: 0 AN: 34114

South Asian (SAS) AF: 0.0000600 AC: 4 AN: 66662

European-Finnish (FIN) AF: 0.0000978 AC: 4 AN: 40910

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4524

European-Non Finnish (NFE) AF: 0.0000856 AC: 71 AN: 829866

Other (OTH) AF: 0.0000432 AC: 2 AN: 46320

⚠️ 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 Cov.: 31

Alfa AF: 0.000186 Hom.: 11

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs369797804; hg19: chr10-21901255;