rs10964552

Variant names:

• chr9-20405632-C-A
• rs10964552
• NM_004529.4:c.1125+8089G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-20405632-C-A
• chr9-20405632-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLLT3	NM_004529.4	c.1125+8089G>T		intron_variant	Intron 5 of 10	ENST00000380338.9	NP_004520.2
MLLT3	NM_001286691.2	c.1116+8089G>T		intron_variant	Intron 5 of 10		NP_001273620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLLT3	ENST00000380338.9	c.1125+8089G>T		intron_variant	Intron 5 of 10	1	NM_004529.4	ENSP00000369695.4
MLLT3	ENST00000630269.2	c.1116+8089G>T		intron_variant	Intron 5 of 10	2		ENSP00000485996.1
MLLT3	ENST00000468513.5	n.257+4929G>T		intron_variant	Intron 2 of 4	3
MLLT3	ENST00000475957.1	n.1082+8089G>T		intron_variant	Intron 3 of 4	2

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

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.0724

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.156

Alfa AF: 0.158 Hom.: 2799

Bravo AF: 0.168

Asia WGS AF: 0.161 AC: 560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.87
DANN	Benign	0.24

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

Publications

LitVar

Other links and lift over

dbSNP: rs10964552; hg19: chr9-20405630;