10-21673318-CTTTTT-C

Position:

• chr10-21673318-CTTTTT-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_001195626.3(MLLT10):​c.1052-14_1052-10del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 307,276 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0015 (0 hom.)
• Consequence: MLLT10 NM_001195626.3 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.414

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 Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 10-21673318-CTTTTT-C is Benign according to our data. Variant chr10-21673318-CTTTTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 3039949.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAdExome4 at 344 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLLT10	NM_001195626.3	c.1052-14_1052-10del		intron_variant		ENST00000307729.12	NP_001182555.1
MLLT10	NM_001324297.2	c.317-14_317-10del		intron_variant			NP_001311226.1
MLLT10	NM_004641.4	c.1052-14_1052-10del		intron_variant			NP_004632.1
MLLT10	NR_136736.2	n.1519-14_1519-10del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLLT10	ENST00000307729.12	c.1052-14_1052-10del		intron_variant		1	NM_001195626.3	ENSP00000307411	P1

Frequencies

GnomAD3 genomes AF: 0.0000126 AC: 1 AN: 79132 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000248

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00151 AC: 344 AN: 228144 Hom.: 0 AF XY: 0.00154 AC XY: 183 AN XY: 119172

Gnomad4 AFR exome AF: 0.00122

Gnomad4 AMR exome AF: 0.00155

Gnomad4 ASJ exome AF: 0.00129

Gnomad4 EAS exome AF: 0.00103

Gnomad4 SAS exome AF: 0.000399

Gnomad4 FIN exome AF: 0.00100

Gnomad4 NFE exome AF: 0.00166

Gnomad4 OTH exome AF: 0.00181

GnomAD4 genome AF: 0.0000126 AC: 1 AN: 79132 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 35944

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000248

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MLLT10-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 09, 2019

This variant is classified as likely 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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs397719980; hg19: chr10-21962247;