NM_004529.4:c.193+35421C>T

Variant names:

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

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-4 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -4 classification points (ACGS-UK Somatic Oncogenicity v2025). B1_Strong

The NM_004529.4(MLLT3):c.193+35421C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The gene MLLT3 is a known oncogene (CancerMine: 1 TSG, 29 oncogene, 280 driver citations). The gene MLLT3 is a cancer driver gene (CancerMine: 1 TSG, 29 oncogene, 280 driver citations). The variant allele was found at a cumulative frequency of 0.405 (AC=61,473) in the gnomAD database across 151,932 control chromosomes, including 13,120 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.489. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. 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 several functions, including chromatin binding activity; histone H3 reader activity; and histone binding activity. Involved in several processes, including hematopoietic stem cell differentiation; positive regulation of DNA-templated transcription; 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 nucleoplasm. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Jun 2026]

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -4 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	B1High frequency in general population		GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.489 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	MLLT3 NM_004529.4	MANE Select	c.193+35421C>T	intron	Intron 2 of 10	Prot: NP_004520.2 UniProt:
	MLLT3 NM_001286691.2		c.184+35421C>T	intron	Intron 2 of 10	Prot: NP_001273620.1 UniProt:

MLLT3 NM_004529.4

MANE Select

HGVSc / HGVSpc.193+35421C>T

Exon rankIntron 2 of 10

intron

Prot: NP_004520.2UniProt: A0A0S2Z448P42568-1

MLLT3 NM_001286691.2

HGVSc / HGVSpc.184+35421C>T

Exon rankIntron 2 of 10

intron

Prot: NP_001273620.1UniProt: P42568-2

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	MLLT3 ENST00000380338.9	TSL:1MANE Select	c.193+35421C>T	intron	Intron 2 of 10	Prot: ENSP00000369695.4 UniProt:
	MLLT3 ENST00000630269.2	TSL:2	c.184+35421C>T	intron	Intron 2 of 10	Prot: ENSP00000485996.1 UniProt:
	MLLT3 ENST00000475957.1	TSL:2	n.377+35421C>T	intron	Intron 2 of 4	Prot:

MLLT3 ENST00000380338.9

TSL:1MANE Select

HGVSc / HGVSpc.193+35421C>T

Exon rankIntron 2 of 10

intron

Prot: ENSP00000369695.4UniProt: P42568-1

MLLT3 ENST00000630269.2

TSL:2

HGVSc / HGVSpc.184+35421C>T

Exon rankIntron 2 of 10

intron

Prot: ENSP00000485996.1UniProt: P42568-2

MLLT3 ENST00000475957.1

TSL:2

HGVSc / HGVSpn.377+35421C>T

Exon rankIntron 2 of 4

intron

Prot:

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.405	AC:61442	Hom:13119	AN:151814	Cov:31
GnomAD4 genome	AF: 0.405	AC:61473	Hom:13120	AN:151932	Cov:31
TOPMed (Bravo)	AF: 0.399	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.441	AC:37552	Hom:8928	AN:85114	Cov:
Local & regional cohorts 9 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.431	AC:996	Hom:218	AN:2310	Cov:
ChinaMAP Phase 1	AF: 0.240	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.427	AC:128	Hom:	AN:300	Cov:
Korea4K (4,157 Koreans)	AF: 0.193	AC:1397	Hom:	AN:7228	Cov:
Qatari Genome	AF: 0.489	AC:86	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.203	AC:24896	Hom:2476	AN:122660	Cov:
Turkish Variome	AF: 0.449	AC:693	Hom:147	AN:1544	Cov:
UK10K	AF: 0.488	AC:3687	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.245	AC:2196	Hom:259	AN:8960	Cov:

Showing 13 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	4.6
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.53
GPN-Star LLR	N/A	0.083
GPN-Star score	N/A	-0.083
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	-0.71

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs4977433;

hg19: chr9-20585232;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar