rs16938057

Variant names:

• chr9-20407936-T-C
• rs16938057
• NM_004529.4:c.1125+5785A>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.1125+5785A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,192 control chromosomes in the GnomAD database, including 1,910 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 0.11 (1910 hom., cov: 32)
• Consequence: MLLT3 NM_004529.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48
• Publications: 1 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLLT3	NM_004529.4	c.1125+5785A>G		intron_variant	Intron 5 of 10	ENST00000380338.9	NP_004520.2
MLLT3	NM_001286691.2	c.1116+5785A>G		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+5785A>G		intron_variant	Intron 5 of 10	1	NM_004529.4	ENSP00000369695.4
MLLT3	ENST00000630269.2	c.1116+5785A>G		intron_variant	Intron 5 of 10	2		ENSP00000485996.1
MLLT3	ENST00000468513.5	n.257+2625A>G		intron_variant	Intron 2 of 4	3
MLLT3	ENST00000475957.1	n.1082+5785A>G		intron_variant	Intron 3 of 4	2

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16484 AN: 152074 Hom.: 1896 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.0487

Gnomad FIN AF: 0.0251

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0164

Gnomad OTH AF: 0.0985

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

GnomAD4 genome AF: 0.109 AC: 16525 AN: 152192 Hom.: 1910 Cov.: 32 AF XY: 0.110 AC XY: 8172 AN XY: 74436

African (AFR) AF: 0.278 AC: 11534 AN: 41468

American (AMR) AF: 0.126 AC: 1934 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0228 AC: 79 AN: 3472

East Asian (EAS) AF: 0.221 AC: 1142 AN: 5170

South Asian (SAS) AF: 0.0485 AC: 234 AN: 4826

European-Finnish (FIN) AF: 0.0251 AC: 267 AN: 10620

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0164 AC: 1117 AN: 68020

Other (OTH) AF: 0.0974 AC: 206 AN: 2114

Alfa AF: 0.0768 Hom.: 241

Bravo AF: 0.125

Asia WGS AF: 0.122 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.7
DANN	Benign	0.73
PhyloP100		1.5
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: rs16938057; hg19: chr9-20407934;