NM_004529.4:c.193+19476C>T

Variant names:

• chr9-20601178-G-A
• rs668703
• NM_004529.4:c.193+19476C>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+19476C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 152,030 control chromosomes in the GnomAD database, including 13,511 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 0.41 (13511 hom., cov: 32)
• Consequence: MLLT3 NM_004529.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.49 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+19476C>T		intron	N/A	NP_004520.2
	MLLT3	NM_001286691.2		c.184+19476C>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+19476C>T		intron	N/A	ENSP00000369695.4
	MLLT3	ENST00000630269.2	TSL:2	c.184+19476C>T		intron	N/A	ENSP00000485996.1
	MLLT3	ENST00000475957.1	TSL:2	n.377+19476C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62568 AN: 151912 Hom.: 13506 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.412 AC: 62609 AN: 152030 Hom.: 13511 Cov.: 32 AF XY: 0.406 AC XY: 30146 AN XY: 74290

African (AFR) AF: 0.305 AC: 12654 AN: 41450

American (AMR) AF: 0.402 AC: 6145 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1625 AN: 3472

East Asian (EAS) AF: 0.263 AC: 1357 AN: 5166

South Asian (SAS) AF: 0.375 AC: 1804 AN: 4816

European-Finnish (FIN) AF: 0.372 AC: 3926 AN: 10540

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.495 AC: 33625 AN: 67990

Other (OTH) AF: 0.430 AC: 908 AN: 2114

Alfa AF: 0.464 Hom.: 48271

Bravo AF: 0.409

Asia WGS AF: 0.351 AC: 1221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.1
DANN	Benign	0.77
PhyloP100		-0.054
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs668703; hg19: chr9-20601177;