NM_004529.4:c.194-57616G>A

Variant names:

• chr9-20514402-C-T
• rs10811359
• NM_004529.4:c.194-57616G>A

Variant summary

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

The NM_004529.4(MLLT3):​c.194-57616G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,810 control chromosomes in the GnomAD database, including 17,645 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 0.48 (17645 hom., cov: 31)
• Consequence: MLLT3 NM_004529.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.844
• Publications: 0 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.616 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.194-57616G>A		intron	N/A	NP_004520.2
	MLLT3	NM_001286691.2		c.185-57616G>A		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.194-57616G>A		intron	N/A	ENSP00000369695.4
	MLLT3	ENST00000630269.2	TSL:2	c.185-57616G>A		intron	N/A	ENSP00000485996.1
	MLLT3	ENST00000475957.1	TSL:2	n.378-99977G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72426 AN: 151690 Hom.: 17627 Cov.: 31

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.477 AC: 72483 AN: 151810 Hom.: 17645 Cov.: 31 AF XY: 0.486 AC XY: 36036 AN XY: 74200

African (AFR) AF: 0.527 AC: 21811 AN: 41360

American (AMR) AF: 0.499 AC: 7619 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1567 AN: 3468

East Asian (EAS) AF: 0.635 AC: 3287 AN: 5180

South Asian (SAS) AF: 0.514 AC: 2463 AN: 4790

European-Finnish (FIN) AF: 0.572 AC: 6028 AN: 10534

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28279 AN: 67908

Other (OTH) AF: 0.467 AC: 986 AN: 2110

Alfa AF: 0.431 Hom.: 24440

Bravo AF: 0.474

Asia WGS AF: 0.530 AC: 1840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.35
DANN	Benign	0.63
PhyloP100		-0.84
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: rs10811359; hg19: chr9-20514400;