9-20413794-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_004529.4(MLLT3):c.1052C>T(p.Thr351Met) variant causes a missense change. The variant allele was found at a frequency of 0.00011 in 1,613,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
MLLT3
NM_004529.4 missense
NM_004529.4 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 4.45
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.15366843).
BS2
?
High AC in GnomAd at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MLLT3 | NM_004529.4 | c.1052C>T | p.Thr351Met | missense_variant | 5/11 | ENST00000380338.9 | |
MLLT3 | NM_001286691.2 | c.1043C>T | p.Thr348Met | missense_variant | 5/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MLLT3 | ENST00000380338.9 | c.1052C>T | p.Thr351Met | missense_variant | 5/11 | 1 | NM_004529.4 | P4 | |
MLLT3 | ENST00000630269.2 | c.1043C>T | p.Thr348Met | missense_variant | 5/11 | 2 | A1 | ||
MLLT3 | ENST00000475957.1 | n.1009C>T | non_coding_transcript_exon_variant | 3/5 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152166Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000677 AC: 17AN: 250992Hom.: 0 AF XY: 0.0000885 AC XY: 12AN XY: 135636
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GnomAD4 exome AF: 0.000112 AC: 164AN: 1461574Hom.: 0 Cov.: 32 AF XY: 0.000124 AC XY: 90AN XY: 727068
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GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74306
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 02, 2021 | The c.1052C>T (p.T351M) alteration is located in exon 5 (coding exon 5) of the MLLT3 gene. This alteration results from a C to T substitution at nucleotide position 1052, causing the threonine (T) at amino acid position 351 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Uncertain
D;D
Polyphen
P;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at