chr10-21673318-CTTT-C

Variant names:

• chr10-21673318-CTTT-C
• rs397719980
• NM_001195626.3:c.1052-12_1052-10delTTT

Variant summary

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

The NM_001195626.3(MLLT10):​c.1052-12_1052-10delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 304,242 control chromosomes in the GnomAD database, including 1 homozygotes. 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00010 (0 hom., cov: 0)
  • Exomes 𝑓: 0.053 (1 hom.)
• Consequence: MLLT10 NM_001195626.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.414
• 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]

ENSG00000304565 (HGNC:):

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.1052-12_1052-10delTTT		intron_variant	Intron 10 of 22	ENST00000307729.12	NP_001182555.1
MLLT10	NM_004641.4	c.1052-12_1052-10delTTT		intron_variant	Intron 10 of 23		NP_004632.1
MLLT10	NM_001324297.2	c.317-12_317-10delTTT		intron_variant	Intron 12 of 24		NP_001311226.1
MLLT10	NR_136736.2	n.1519-12_1519-10delTTT		intron_variant	Intron 11 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLLT10	ENST00000307729.12	c.1052-31_1052-29delTTT		intron_variant	Intron 10 of 22	1	NM_001195626.3	ENSP00000307411.7

Frequencies

GnomAD3 genomes AF: 0.000101 AC: 8 AN: 79124 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000315

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000124

Gnomad OTH AF: 0.00102

GnomAD4 exome AF: 0.0525 AC: 11828 AN: 225118 Hom.: 1 AF XY: 0.0524 AC XY: 6151 AN XY: 117474

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

African (AFR) AF: 0.0432 AC: 208 AN: 4820

American (AMR) AF: 0.0385 AC: 362 AN: 9408

Ashkenazi Jewish (ASJ) AF: 0.0617 AC: 284 AN: 4606

East Asian (EAS) AF: 0.0354 AC: 406 AN: 11454

South Asian (SAS) AF: 0.0247 AC: 305 AN: 12362

European-Finnish (FIN) AF: 0.0372 AC: 512 AN: 13774

Middle Eastern (MID) AF: 0.0668 AC: 49 AN: 734

European-Non Finnish (NFE) AF: 0.0577 AC: 9089 AN: 157568

Other (OTH) AF: 0.0590 AC: 613 AN: 10392

⚠️ 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: 0.000101 AC: 8 AN: 79124 Hom.: 0 Cov.: 0 AF XY: 0.0000835 AC XY: 3 AN XY: 35940

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

African (AFR) AF: 0.00 AC: 0 AN: 22074

American (AMR) AF: 0.000315 AC: 2 AN: 6352

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2204

East Asian (EAS) AF: 0.00 AC: 0 AN: 2474

South Asian (SAS) AF: 0.00 AC: 0 AN: 1848

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2122

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 150

European-Non Finnish (NFE) AF: 0.000124 AC: 5 AN: 40364

Other (OTH) AF: 0.00102 AC: 1 AN: 978

⚠️ 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: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.41
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: rs397719980; hg19: chr10-21962247;