rs7098100

Positions:

• chr10-21545607-G-A

Variant summary

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

The NM_001195626.3(MLLT10):​c.240+6695G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 151,968 control chromosomes in the GnomAD database, including 11,600 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 0.38 (11600 hom., cov: 32)
• Consequence: MLLT10 NM_001195626.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLLT10	NM_001195626.3	c.240+6695G>A		intron_variant		ENST00000307729.12	NP_001182555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLLT10	ENST00000307729.12	c.240+6695G>A		intron_variant		1	NM_001195626.3	ENSP00000307411	P1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56964 AN: 151850 Hom.: 11565 Cov.: 32

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.0485

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.375 AC: 57051 AN: 151968 Hom.: 11600 Cov.: 32 AF XY: 0.370 AC XY: 27475 AN XY: 74290

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.0482

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.419

Alfa AF: 0.370 Hom.: 3115

Bravo AF: 0.380

Asia WGS AF: 0.216 AC: 754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.27
DANN	Benign	0.77

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: rs7098100; hg19: chr10-21834536;