NM_004529.4:c.193+38097G>A

Variant names:

• chr9-20582557-C-T
• rs4621895
• NM_004529.4:c.193+38097G>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.193+38097G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 151,894 control chromosomes in the GnomAD database, including 13,810 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 0.42 (13810 hom., cov: 32)
• Consequence: MLLT3 NM_004529.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLLT3	NM_004529.4	c.193+38097G>A		intron_variant	Intron 2 of 10	ENST00000380338.9	NP_004520.2
MLLT3	NM_001286691.2	c.184+38097G>A		intron_variant	Intron 2 of 10		NP_001273620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLLT3	ENST00000380338.9	c.193+38097G>A		intron_variant	Intron 2 of 10	1	NM_004529.4	ENSP00000369695.4
MLLT3	ENST00000630269.2	c.184+38097G>A		intron_variant	Intron 2 of 10	2		ENSP00000485996.1
MLLT3	ENST00000475957.1	n.377+38097G>A		intron_variant	Intron 2 of 4	2

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63574 AN: 151776 Hom.: 13809 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.419 AC: 63605 AN: 151894 Hom.: 13810 Cov.: 32 AF XY: 0.412 AC XY: 30555 AN XY: 74230

African (AFR) AF: 0.349 AC: 14444 AN: 41390

American (AMR) AF: 0.373 AC: 5693 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1617 AN: 3464

East Asian (EAS) AF: 0.228 AC: 1180 AN: 5172

South Asian (SAS) AF: 0.368 AC: 1771 AN: 4810

European-Finnish (FIN) AF: 0.371 AC: 3908 AN: 10534

Middle Eastern (MID) AF: 0.503 AC: 147 AN: 292

European-Non Finnish (NFE) AF: 0.493 AC: 33528 AN: 67950

Other (OTH) AF: 0.425 AC: 894 AN: 2106

Alfa AF: 0.446 Hom.: 7734

Bravo AF: 0.415

Asia WGS AF: 0.331 AC: 1150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.39
DANN	Benign	0.16
PhyloP100		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs4621895; hg19: chr9-20582556; COSMIC: COSV63496239;