chr19-6213079-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005934.4(MLLT1):​c.1643G>A​(p.Arg548His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

MLLT1
NM_005934.4 missense

Scores

5
7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.54
Variant links:
Genes affected
MLLT1 (HGNC:7134): (MLLT1 super elongation complex subunit) Predicted to be involved in regulation of transcription, DNA-templated. Predicted to act upstream of or within negative regulation of protein kinase activity. Located in cytosol; fibrillar center; 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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MLLT1NM_005934.4 linkc.1643G>A p.Arg548His missense_variant Exon 12 of 12 ENST00000252674.9 NP_005925.2 Q03111

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MLLT1ENST00000252674.9 linkc.1643G>A p.Arg548His missense_variant Exon 12 of 12 1 NM_005934.4 ENSP00000252674.6 Q03111
MLLT1ENST00000585588.1 linkn.*41G>A downstream_gene_variant 3 ENSP00000519594.1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Jan 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

MLLT1: PM2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.31
BayesDel_addAF
Uncertain
0.062
T
BayesDel_noAF
Benign
-0.15
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.61
D
Eigen
Pathogenic
0.73
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Benign
0.083
D
MetaRNN
Uncertain
0.66
D
MetaSVM
Uncertain
-0.058
T
MutationAssessor
Benign
1.3
L
PrimateAI
Pathogenic
0.84
D
PROVEAN
Benign
-2.3
N
REVEL
Benign
0.20
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0090
D
Polyphen
1.0
D
Vest4
0.65
MutPred
0.34
Gain of catalytic residue at L550 (P = 0.1074);
MVP
0.50
MPC
2.3
ClinPred
0.97
D
GERP RS
4.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.43
gMVP
0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-6213090; COSMIC: COSV105007057; COSMIC: COSV105007057; API