rs1243188

chr10-21619874-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001195626.3(MLLT10):c.699+2667T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 151,786 control chromosomes in the GnomAD database, including 8,510 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (8510 hom., cov: 31)
• Consequence: MLLT10 NM_001195626.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.83

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MLLT10	NM_001195626.3	c.699+2667T>C		intron_variant		ENST00000307729.12
MLLT10	NM_001324297.2	c.-173+2667T>C		intron_variant
MLLT10	NM_004641.4	c.699+2667T>C		intron_variant
MLLT10	NR_136736.2	n.1166+2667T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLLT10	ENST00000307729.12	c.699+2667T>C		intron_variant		1	NM_001195626.3	P1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49386 AN: 151670 Hom.: 8474 Cov.: 31

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.0223

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.355

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.326 AC: 49478 AN: 151786 Hom.: 8510 Cov.: 31 AF XY: 0.322 AC XY: 23914 AN XY: 74202

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.0222

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.359

Alfa AF: 0.319 Hom.: 13663

Bravo AF: 0.334

Asia WGS AF: 0.178 AC: 619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.058
Dann	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs1243188; hg19: chr10-21908803;