9-20536299-T-G

Variant names:

• chr9-20536299-T-G
• rs7037941
• NM_004529.4:c.194-79513A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004529.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLLT3	NM_004529.4	MANE Select	c.194-79513A>C		intron	N/A	NP_004520.2	A0A0S2Z448
	MLLT3	NM_001286691.2		c.185-79513A>C		intron	N/A	NP_001273620.1	P42568-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLLT3	ENST00000380338.9	TSL:1 MANE Select	c.194-79513A>C		intron	N/A	ENSP00000369695.4	P42568-1
	MLLT3	ENST00000630269.2	TSL:2	c.185-79513A>C		intron	N/A	ENSP00000485996.1	P42568-2
	MLLT3	ENST00000475957.1	TSL:2	n.377+84355A>C		intron	N/A

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

African (AFR) AF: 0.402 AC: 16642 AN: 41442

American (AMR) AF: 0.465 AC: 7113 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1836 AN: 3466

East Asian (EAS) AF: 0.526 AC: 2719 AN: 5170

South Asian (SAS) AF: 0.520 AC: 2502 AN: 4816

European-Finnish (FIN) AF: 0.597 AC: 6310 AN: 10566

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.443 AC: 30129 AN: 67962

Other (OTH) AF: 0.459 AC: 970 AN: 2112

Alfa AF: 0.366 Hom.: 1530

Bravo AF: 0.439

Asia WGS AF: 0.510 AC: 1768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.50
PhyloP100		-0.064
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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