9-20585233-G-T

Variant names:

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

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-2 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -2 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Strong

The NM_004529.4(MLLT3):c.193+35421C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. 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: not found (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 ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: unknown) (threshold 0.001) — PM2 moderate.
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

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>A	intron	Intron 2 of 10	Prot: NP_004520.2 UniProt:
	MLLT3 NM_001286691.2		c.184+35421C>A	intron	Intron 2 of 10	Prot: NP_001273620.1 UniProt:

MLLT3 NM_004529.4

MANE Select

HGVSc / HGVSpc.193+35421C>A

Exon rankIntron 2 of 10

intron

Prot: NP_004520.2UniProt: A0A0S2Z448P42568-1

MLLT3 NM_001286691.2

HGVSc / HGVSpc.184+35421C>A

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>A	intron	Intron 2 of 10	Prot: ENSP00000369695.4 UniProt:
	MLLT3 ENST00000630269.2	TSL:2	c.184+35421C>A	intron	Intron 2 of 10	Prot: ENSP00000485996.1 UniProt:
	MLLT3 ENST00000475957.1	TSL:2	n.377+35421C>A	intron	Intron 2 of 4	Prot:

MLLT3 ENST00000380338.9

TSL:1MANE Select

HGVSc / HGVSpc.193+35421C>A

Exon rankIntron 2 of 10

intron

Prot: ENSP00000369695.4UniProt: P42568-1

MLLT3 ENST00000630269.2

TSL:2

HGVSc / HGVSpc.184+35421C>A

Exon rankIntron 2 of 10

intron

Prot: ENSP00000485996.1UniProt: P42568-2

MLLT3 ENST00000475957.1

TSL:2

HGVSc / HGVSpn.377+35421C>A

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 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:31
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:31
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00	AC:0	Hom:8928	AN:85114	Cov:

Showing 3 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	5.8
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.33
DANN	Benign	0.47
GPN-Star LLR	N/A	0.27
GPN-Star score	N/A	-0.27
PhyloP100	Benign	-0.71

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Uncertain	0.45
Pangolin gain	Uncertain	0.45	Position offset: -2
SpliceAI score (max)	Benign	0.030	Details are displayed if max score is > 0.2

Showing 3 of 3 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