10-21538867-G-A

Variant names:

• chr10-21538867-G-A
• rs1802669
• NM_001195626.3:c.195G>A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001324297.2(MLLT10):​c.-881G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,609,888 control chromosomes in the GnomAD database, including 93,421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.35 (9870 hom., cov: 32)
  • Exomes 𝑓: 0.33 (83551 hom.)
• Consequence: MLLT10 NM_001324297.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.309

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 10-21538867-G-A is Benign according to our data. Variant chr10-21538867-G-A is described in ClinVar as [Benign]. Clinvar id is 3055784.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr10-21538867-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLLT10	NM_001195626.3	c.195G>A	p.Pro65Pro	synonymous_variant	Exon 3 of 23	ENST00000307729.12	NP_001182555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLLT10	ENST00000307729.12	c.195G>A	p.Pro65Pro	synonymous_variant	Exon 3 of 23	1	NM_001195626.3	ENSP00000307411.7

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53130 AN: 151866 Hom.: 9850 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.0492

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.401

GnomAD3 exomes AF: 0.306 AC: 76762 AN: 250928 Hom.: 13239 AF XY: 0.310 AC XY: 42012 AN XY: 135638

Gnomad AFR exome AF: 0.399

Gnomad AMR exome AF: 0.213

Gnomad ASJ exome AF: 0.422

Gnomad EAS exome AF: 0.0443

Gnomad SAS exome AF: 0.255

Gnomad FIN exome AF: 0.327

Gnomad NFE exome AF: 0.361

Gnomad OTH exome AF: 0.338

GnomAD4 exome AF: 0.331 AC: 482322 AN: 1457904 Hom.: 83551 Cov.: 31 AF XY: 0.330 AC XY: 239173 AN XY: 725412

Gnomad4 AFR exome AF: 0.416

Gnomad4 AMR exome AF: 0.228

Gnomad4 ASJ exome AF: 0.423

Gnomad4 EAS exome AF: 0.0350

Gnomad4 SAS exome AF: 0.258

Gnomad4 FIN exome AF: 0.322

Gnomad4 NFE exome AF: 0.346

Gnomad4 OTH exome AF: 0.340

GnomAD4 genome AF: 0.350 AC: 53201 AN: 151984 Hom.: 9870 Cov.: 32 AF XY: 0.345 AC XY: 25655 AN XY: 74272

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.0489

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.404

Alfa AF: 0.344 Hom.: 5838

Bravo AF: 0.350

Asia WGS AF: 0.218 AC: 761 AN: 3478

EpiCase AF: 0.378

EpiControl AF: 0.379

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MLLT10-related disorder Benign:1

Sep 24, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	11
DANN	Benign	0.55
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6

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: rs1802669; hg19: chr10-21827796; COSMIC: COSV57005677;