chr9-20586401-G-A

Variant names:

• chr9-20586401-G-A
• rs10757142
• NM_004529.4:c.193+34253C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004529.4(MLLT3):​c.193+34253C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 135,678 control chromosomes in the GnomAD database, including 24,360 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 0.62 (24360 hom., cov: 24)
• Consequence: MLLT3 NM_004529.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.705 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLLT3	NM_004529.4	MANE Select	c.193+34253C>T		intron	N/A	NP_004520.2
	MLLT3	NM_001286691.2		c.184+34253C>T		intron	N/A	NP_001273620.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLLT3	ENST00000380338.9	TSL:1 MANE Select	c.193+34253C>T		intron	N/A	ENSP00000369695.4
	MLLT3	ENST00000630269.2	TSL:2	c.184+34253C>T		intron	N/A	ENSP00000485996.1
	MLLT3	ENST00000475957.1	TSL:2	n.377+34253C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.619 AC: 83987 AN: 135624 Hom.: 24376 Cov.: 24

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.757

Gnomad NFE AF: 0.710

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.619 AC: 83978 AN: 135678 Hom.: 24360 Cov.: 24 AF XY: 0.619 AC XY: 40616 AN XY: 65650

African (AFR) AF: 0.463 AC: 17937 AN: 38700

American (AMR) AF: 0.590 AC: 8109 AN: 13740

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2170 AN: 3106

East Asian (EAS) AF: 0.575 AC: 2869 AN: 4988

South Asian (SAS) AF: 0.726 AC: 3189 AN: 4390

European-Finnish (FIN) AF: 0.649 AC: 4947 AN: 7618

Middle Eastern (MID) AF: 0.750 AC: 201 AN: 268

European-Non Finnish (NFE) AF: 0.710 AC: 42671 AN: 60110

Other (OTH) AF: 0.630 AC: 1186 AN: 1884

Alfa AF: 0.785 Hom.: 91511

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.25
DANN	Benign	0.30
PhyloP100		-0.065
Mutation Taster		=9/91	disease causing

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: rs10757142; hg19: chr9-20586400;