10-21673318-CTTTTTTTTTTTT-CTTTTTTTTTTTTTT

Variant names:

• chr10-21673318-C-CTT
• rs397719980
• NM_001195626.3:c.1052-11_1052-10dupTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001195626.3(MLLT10):​c.1052-11_1052-10dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0018 (0 hom.)
• Consequence: MLLT10 NM_001195626.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLLT10	NM_001195626.3	c.1052-11_1052-10dupTT		intron_variant	Intron 10 of 22	ENST00000307729.12	NP_001182555.1
MLLT10	NM_004641.4	c.1052-11_1052-10dupTT		intron_variant	Intron 10 of 23		NP_004632.1
MLLT10	NM_001324297.2	c.317-11_317-10dupTT		intron_variant	Intron 12 of 24		NP_001311226.1
MLLT10	NR_136736.2	n.1519-11_1519-10dupTT		intron_variant	Intron 11 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLLT10	ENST00000307729.12	c.1052-32_1052-31insTT		intron_variant	Intron 10 of 22	1	NM_001195626.3	ENSP00000307411.7

Frequencies

GnomAD3 genomes AF: 0.000126 AC: 10 AN: 79126 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000404

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000124

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00177 AC: 404 AN: 228202 Hom.: 0 Cov.: 0 AF XY: 0.00166 AC XY: 198 AN XY: 119192

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

African (AFR) AF: 0.00244 AC: 12 AN: 4908

American (AMR) AF: 0.00135 AC: 13 AN: 9656

Ashkenazi Jewish (ASJ) AF: 0.00129 AC: 6 AN: 4656

East Asian (EAS) AF: 0.00300 AC: 35 AN: 11656

South Asian (SAS) AF: 0.00120 AC: 15 AN: 12536

European-Finnish (FIN) AF: 0.000858 AC: 12 AN: 13978

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 746

European-Non Finnish (NFE) AF: 0.00177 AC: 283 AN: 159534

Other (OTH) AF: 0.00266 AC: 28 AN: 10532

⚠️ 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: 0.000126 AC: 10 AN: 79126 Hom.: 0 Cov.: 0 AF XY: 0.000139 AC XY: 5 AN XY: 35956

African (AFR) AF: 0.000181 AC: 4 AN: 22084

American (AMR) AF: 0.00 AC: 0 AN: 6358

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

East Asian (EAS) AF: 0.000406 AC: 1 AN: 2466

South Asian (SAS) AF: 0.00 AC: 0 AN: 1846

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 138

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

Other (OTH) AF: 0.00 AC: 0 AN: 986

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.5

Splicing

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

Other links and lift over

dbSNP: rs397719980; hg19: chr10-21962247;