9-20536299-T-G

Position:

• chr9-20536299-T-G

Variant summary

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

The NM_004529.4(MLLT3):​c.194-79513A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,028 control chromosomes in the GnomAD database, including 15,762 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 0.45 (15762 hom., cov: 32)
• Consequence: MLLT3 NM_004529.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MLLT3	NM_004529.4	c.194-79513A>C		intron_variant		ENST00000380338.9
MLLT3	NM_001286691.2	c.185-79513A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLLT3	ENST00000380338.9	c.194-79513A>C		intron_variant		1	NM_004529.4	P4
MLLT3	ENST00000630269.2	c.185-79513A>C		intron_variant		2		A1
MLLT3	ENST00000475957.1	n.377+84355A>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68657 AN: 151910 Hom.: 15759 Cov.: 32

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.452 AC: 68695 AN: 152028 Hom.: 15762 Cov.: 32 AF XY: 0.460 AC XY: 34152 AN XY: 74312

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.597

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.459

Alfa AF: 0.363 Hom.: 1463

Bravo AF: 0.439

Asia WGS AF: 0.510 AC: 1768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.50

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: rs7037941; hg19: chr9-20536297; COSMIC: COSV63496103; COSMIC: COSV63496103;