GeneBe

rs1344480038

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138792.4(LEO1):​c.1955A>T​(p.His652Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H652P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

LEO1
NM_138792.4 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.50
Variant links:
Genes affected
LEO1 (HGNC:30401): (LEO1 homolog, Paf1/RNA polymerase II complex component) LEO1, parafibromin (CDC73; MIM 607393), CTR9 (MIM 609366), and PAF1 (MIM 610506) form the PAF protein complex that associates with the RNA polymerase II subunit POLR2A (MIM 180660) and with a histone methyltransferase complex (Rozenblatt-Rosen et al., 2005 [PubMed 15632063]).[supplied by OMIM, Mar 2008]
TMOD3 (HGNC:11873): (tropomodulin 3) Enables cadherin binding activity involved in cell-cell adhesion. Predicted to be involved in actin filament organization; muscle contraction; and myofibril assembly. Predicted to act upstream of or within actin cytoskeleton organization; erythrocyte development; and positive regulation of mitotic cell cycle phase transition. Located in adherens junction. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.114061505).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LEO1NM_138792.4 linkc.1955A>T p.His652Leu missense_variant Exon 12 of 12 ENST00000299601.10 NP_620147.1 Q8WVC0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LEO1ENST00000299601.10 linkc.1955A>T p.His652Leu missense_variant Exon 12 of 12 1 NM_138792.4 ENSP00000299601.5 Q8WVC0-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1458720
Hom.:
0
Cov.:
28
AF XY:
0.00000138
AC XY:
1
AN XY:
725844
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.082
BayesDel_addAF
Benign
-0.026
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
21
DANN
Benign
0.97
DEOGEN2
Benign
0.23
T;.
Eigen
Benign
-0.21
Eigen_PC
Benign
-0.028
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.0041
T
MetaRNN
Benign
0.11
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N;.
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-1.1
N;N
REVEL
Benign
0.029
Sift
Benign
0.10
T;D
Sift4G
Benign
0.34
T;T
Polyphen
0.080
B;B
Vest4
0.33
MutPred
0.13
Loss of loop (P = 0.0374);.;
MVP
0.35
MPC
1.1
ClinPred
0.75
D
GERP RS
4.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.14
gMVP
0.066

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: chr15-52230399; API