rs4977433

Variant names:

• chr9-20585233-G-A
• rs4977433
• NM_004529.4:c.193+35421C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-20585233-G-A
• chr9-20585233-G-C
• chr9-20585233-G-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+35421C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,932 control chromosomes in the GnomAD database, including 13,120 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 0.40 (13120 hom., cov: 31)
• Consequence: MLLT3 NM_004529.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.715
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.489 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+35421C>T		intron	N/A	NP_004520.2
	MLLT3	NM_001286691.2		c.184+35421C>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+35421C>T		intron	N/A	ENSP00000369695.4
	MLLT3	ENST00000630269.2	TSL:2	c.184+35421C>T		intron	N/A	ENSP00000485996.1
	MLLT3	ENST00000475957.1	TSL:2	n.377+35421C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61442 AN: 151814 Hom.: 13119 Cov.: 31

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.405 AC: 61473 AN: 151932 Hom.: 13120 Cov.: 31 AF XY: 0.398 AC XY: 29566 AN XY: 74256

African (AFR) AF: 0.301 AC: 12447 AN: 41400

American (AMR) AF: 0.367 AC: 5599 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1621 AN: 3468

East Asian (EAS) AF: 0.229 AC: 1185 AN: 5186

South Asian (SAS) AF: 0.366 AC: 1764 AN: 4814

European-Finnish (FIN) AF: 0.371 AC: 3911 AN: 10536

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.493 AC: 33504 AN: 67948

Other (OTH) AF: 0.416 AC: 875 AN: 2104

Alfa AF: 0.445 Hom.: 7615

Bravo AF: 0.399

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.53
PhyloP100		-0.71
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: rs4977433; hg19: chr9-20585232;