rs12350051

Variant names:

• chr9-20475178-T-C
• rs12350051
• NM_004529.4:c.194-18392A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004529.4(MLLT3):​c.194-18392A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 151,996 control chromosomes in the GnomAD database, including 3,651 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 0.21 (3651 hom., cov: 32)
• Consequence: MLLT3 NM_004529.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149
• Publications: 6 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=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLLT3	NM_004529.4	c.194-18392A>G		intron_variant	Intron 2 of 10	ENST00000380338.9	NP_004520.2
MLLT3	NM_001286691.2	c.185-18392A>G		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.194-18392A>G		intron_variant	Intron 2 of 10	1	NM_004529.4	ENSP00000369695.4
MLLT3	ENST00000630269.2	c.185-18392A>G		intron_variant	Intron 2 of 10	2		ENSP00000485996.1
MLLT3	ENST00000475957.1	n.378-60753A>G		intron_variant	Intron 2 of 4	2

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32627 AN: 151878 Hom.: 3650 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.215 AC: 32645 AN: 151996 Hom.: 3651 Cov.: 32 AF XY: 0.212 AC XY: 15790 AN XY: 74340

African (AFR) AF: 0.176 AC: 7319 AN: 41496

American (AMR) AF: 0.208 AC: 3162 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 943 AN: 3464

East Asian (EAS) AF: 0.133 AC: 689 AN: 5188

South Asian (SAS) AF: 0.245 AC: 1179 AN: 4814

European-Finnish (FIN) AF: 0.209 AC: 2210 AN: 10592

Middle Eastern (MID) AF: 0.247 AC: 72 AN: 292

European-Non Finnish (NFE) AF: 0.242 AC: 16462 AN: 67896

Other (OTH) AF: 0.229 AC: 483 AN: 2112

Alfa AF: 0.232 Hom.: 10404

Bravo AF: 0.209

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.75
PhyloP100		0.15
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: rs12350051; hg19: chr9-20475176; COSMIC: COSV63496010;