9-20414378-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_004529.4(MLLT3):c.468T>C(p.Ser156=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0807 in 144,612 control chromosomes in the GnomAD database, including 468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.081 (468 hom., cov: 32)
  • Exomes 𝑓: 0.030 (965 hom.)
  • Failed GnomAD Quality Control
• Consequence: MLLT3 NM_004529.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.08

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-20414378-A-G is Benign according to our data. Variant chr9-20414378-A-G is described in ClinVar as [Benign]. Clinvar id is 770580.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.08 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MLLT3	NM_004529.4	c.468T>C	p.Ser156=	synonymous_variant	5/11	ENST00000380338.9
MLLT3	NM_001286691.2	c.459T>C	p.Ser153=	synonymous_variant	5/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLLT3	ENST00000380338.9	c.468T>C	p.Ser156=	synonymous_variant	5/11	1	NM_004529.4	P4
MLLT3	ENST00000630269.2	c.459T>C	p.Ser153=	synonymous_variant	5/11	2		A1
MLLT3	ENST00000475957.1	n.425T>C		non_coding_transcript_exon_variant	3/5	2

Frequencies

GnomAD3 genomes AF: 0.0806 AC: 11653 AN: 144494 Hom.: 468 Cov.: 32

Gnomad AFR AF: 0.0905

Gnomad AMI AF: 0.0317

Gnomad AMR AF: 0.0663

Gnomad ASJ AF: 0.0520

Gnomad EAS AF: 0.0273

Gnomad SAS AF: 0.0851

Gnomad FIN AF: 0.0914

Gnomad MID AF: 0.0948

Gnomad NFE AF: 0.0823

Gnomad OTH AF: 0.0758

GnomAD3 exomes AF: 0.0295 AC: 5146 AN: 174546 Hom.: 146 AF XY: 0.0269 AC XY: 2574 AN XY: 95678

Gnomad AFR exome AF: 0.0492

Gnomad AMR exome AF: 0.0242

Gnomad ASJ exome AF: 0.0151

Gnomad EAS exome AF: 0.0141

Gnomad SAS exome AF: 0.0236

Gnomad FIN exome AF: 0.0514

Gnomad NFE exome AF: 0.0304

Gnomad OTH exome AF: 0.0376

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0298 AC: 37301 AN: 1250356 Hom.: 965 Cov.: 34 AF XY: 0.0320 AC XY: 20004 AN XY: 625116

Gnomad4 AFR exome AF: 0.0403

Gnomad4 AMR exome AF: 0.0275

Gnomad4 ASJ exome AF: 0.0309

Gnomad4 EAS exome AF: 0.0248

Gnomad4 SAS exome AF: 0.0459

Gnomad4 FIN exome AF: 0.0702

Gnomad4 NFE exome AF: 0.0260

Gnomad4 OTH exome AF: 0.0380

GnomAD4 genome AF: 0.0807 AC: 11668 AN: 144612 Hom.: 468 Cov.: 32 AF XY: 0.0791 AC XY: 5585 AN XY: 70584

Gnomad4 AFR AF: 0.0907

Gnomad4 AMR AF: 0.0660

Gnomad4 ASJ AF: 0.0520

Gnomad4 EAS AF: 0.0274

Gnomad4 SAS AF: 0.0858

Gnomad4 FIN AF: 0.0914

Gnomad4 NFE AF: 0.0823

Gnomad4 OTH AF: 0.0775

Alfa AF: 0.0852 Hom.: 35

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 30, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.16
Dann	Benign	0.50

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: rs1761445; hg19: chr9-20414376; COSMIC: COSV63494875; COSMIC: COSV63494875;