chr9-20597577-A-C

Variant names:

• chr9-20597577-A-C
• rs6475464
• NM_004529.4:c.193+23077T>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.193+23077T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 151,966 control chromosomes in the GnomAD database, including 7,482 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 0.30 (7482 hom., cov: 32)
• Consequence: MLLT3 NM_004529.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.292
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLLT3	NM_004529.4	c.193+23077T>G		intron_variant	Intron 2 of 10	ENST00000380338.9	NP_004520.2
MLLT3	NM_001286691.2	c.184+23077T>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.193+23077T>G		intron_variant	Intron 2 of 10	1	NM_004529.4	ENSP00000369695.4
MLLT3	ENST00000630269.2	c.184+23077T>G		intron_variant	Intron 2 of 10	2		ENSP00000485996.1
MLLT3	ENST00000475957.1	n.377+23077T>G		intron_variant	Intron 2 of 4	2

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45949 AN: 151848 Hom.: 7479 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.302 AC: 45958 AN: 151966 Hom.: 7482 Cov.: 32 AF XY: 0.308 AC XY: 22891 AN XY: 74288

African (AFR) AF: 0.181 AC: 7490 AN: 41480

American (AMR) AF: 0.287 AC: 4381 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1126 AN: 3470

East Asian (EAS) AF: 0.366 AC: 1892 AN: 5168

South Asian (SAS) AF: 0.431 AC: 2078 AN: 4816

European-Finnish (FIN) AF: 0.415 AC: 4367 AN: 10516

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23429 AN: 67920

Other (OTH) AF: 0.309 AC: 653 AN: 2114

Alfa AF: 0.331 Hom.: 36011

Bravo AF: 0.282

Asia WGS AF: 0.388 AC: 1346 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.69
PhyloP100		-0.29
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: rs6475464; hg19: chr9-20597576; COSMIC: COSV63501241;