rs1243188

Variant names:

• chr10-21619874-T-C
• rs1243188
• NM_001195626.3:c.699+2667T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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 -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 rank	MANE	Protein	UniProt
MLLT10	NM_001195626.3	c.699+2667T>C		intron_variant	Intron 8 of 22	ENST00000307729.12	NP_001182555.1
MLLT10	NM_004641.4	c.699+2667T>C		intron_variant	Intron 8 of 23		NP_004632.1
MLLT10	NM_001324297.2	c.-173+2667T>C		intron_variant	Intron 9 of 24		NP_001311226.1
MLLT10	NR_136736.2	n.1166+2667T>C		intron_variant	Intron 9 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLLT10	ENST00000307729.12	c.699+2667T>C		intron_variant	Intron 8 of 22	1	NM_001195626.3	ENSP00000307411.7

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

African (AFR) AF: 0.401 AC: 16593 AN: 41394

American (AMR) AF: 0.340 AC: 5177 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1304 AN: 3470

East Asian (EAS) AF: 0.0222 AC: 115 AN: 5182

South Asian (SAS) AF: 0.203 AC: 978 AN: 4820

European-Finnish (FIN) AF: 0.296 AC: 3091 AN: 10452

Middle Eastern (MID) AF: 0.483 AC: 141 AN: 292

European-Non Finnish (NFE) AF: 0.308 AC: 20889 AN: 67918

Other (OTH) AF: 0.359 AC: 758 AN: 2110

Alfa AF: 0.316 Hom.: 29153

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
PhyloP100		-2.8
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: rs1243188; hg19: chr10-21908803;