rs1537073

Positions:

• chr9-20528548-A-G

Variant summary

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

The ENST00000380338.9(MLLT3):​c.194-71762T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 152,124 control chromosomes in the GnomAD database, including 19,802 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 0.51 (19802 hom., cov: 33)
• Consequence: MLLT3 ENST00000380338.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

Genes affected

MLLT3 (HGNC:7136): (MLLT3 super elongation complex subunit) Enables chromatin binding activity and lysine-acetylated histone binding activity. Involved in several processes, including hematopoietic stem cell differentiation; positive regulation of transcription, DNA-templated; and regulation of stem cell division. Acts upstream of or within negative regulation of canonical Wnt signaling pathway and positive regulation of Wnt signaling pathway, planar cell polarity pathway. Located in cytosol and nucleoplasm. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLLT3	NM_004529.4	c.194-71762T>C		intron_variant		ENST00000380338.9	NP_004520.2
MLLT3	NM_001286691.2	c.185-71762T>C		intron_variant			NP_001273620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLLT3	ENST00000380338.9	c.194-71762T>C		intron_variant		1	NM_004529.4	ENSP00000369695	P4
MLLT3	ENST00000630269.2	c.185-71762T>C		intron_variant		2		ENSP00000485996	A1
MLLT3	ENST00000475957.1	n.377+92106T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76768 AN: 152006 Hom.: 19784 Cov.: 33

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.505 AC: 76829 AN: 152124 Hom.: 19802 Cov.: 33 AF XY: 0.513 AC XY: 38137 AN XY: 74332

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.601

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.504

Alfa AF: 0.460 Hom.: 15034

Bravo AF: 0.502

Asia WGS AF: 0.569 AC: 1976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.64

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: rs1537073; hg19: chr9-20528546; COSMIC: COSV63496058; COSMIC: COSV63496058;