9-20405632-C-A

Variant names:

• chr9-20405632-C-A
• rs10964552
• NM_004529.4:c.1125+8089G>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.1125+8089G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,142 control chromosomes in the GnomAD database, including 2,412 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 0.17 (2412 hom., cov: 32)
• Consequence: MLLT3 NM_004529.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.463
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLLT3	NM_004529.4	MANE Select	c.1125+8089G>T		intron	N/A	NP_004520.2	A0A0S2Z448
	MLLT3	NM_001286691.2		c.1116+8089G>T		intron	N/A	NP_001273620.1	P42568-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLLT3	ENST00000380338.9	TSL:1 MANE Select	c.1125+8089G>T		intron	N/A	ENSP00000369695.4	P42568-1
	MLLT3	ENST00000630269.2	TSL:2	c.1116+8089G>T		intron	N/A	ENSP00000485996.1	P42568-2
	MLLT3	ENST00000468513.5	TSL:3	n.257+4929G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26410 AN: 152024 Hom.: 2405 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.0720

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.174 AC: 26433 AN: 152142 Hom.: 2412 Cov.: 32 AF XY: 0.172 AC XY: 12824 AN XY: 74374

African (AFR) AF: 0.208 AC: 8620 AN: 41500

American (AMR) AF: 0.132 AC: 2023 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 566 AN: 3470

East Asian (EAS) AF: 0.0724 AC: 375 AN: 5182

South Asian (SAS) AF: 0.193 AC: 932 AN: 4820

European-Finnish (FIN) AF: 0.179 AC: 1888 AN: 10576

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11480 AN: 67988

Other (OTH) AF: 0.156 AC: 330 AN: 2112

Alfa AF: 0.161 Hom.: 4289

Bravo AF: 0.168

Asia WGS AF: 0.161 AC: 560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.87
DANN	Benign	0.24
PhyloP100		-0.46
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: rs10964552; hg19: chr9-20405630;