12-98527937-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001032283.3(TMPO):​c.331G>T​(p.Asp111Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TMPO
NM_001032283.3 missense

Scores

5
11
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.51
Variant links:
Genes affected
TMPO (HGNC:11875): (thymopoietin) Through alternative splicing, this gene encodes several distinct LEM domain containing protein isoforms. LEM domain proteins include inner nuclear membrane and intranuclear proteins, and are involved in a variety of cellular functions including gene expression, chromatin organization, and replication and cell cycle control. The encoded alpha isoform is broadly diffuse in the nucleus and contains a lamin binding domain, while the beta and gamma isoforms are localized to the nuclear membrane and contain an HDAC3 interaction domain. The distinct isoforms may compete with each other when acting to chaperone other proteins and regulate transcription. [provided by RefSeq, Aug 2019]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.794

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TMPONM_001032283.3 linkc.331G>T p.Asp111Tyr missense_variant 2/9 ENST00000556029.6 NP_001027454.1 P42167-1A0A024RBE7Q59G12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMPOENST00000556029.6 linkc.331G>T p.Asp111Tyr missense_variant 2/91 NM_001032283.3 ENSP00000450627.1 P42167-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251398
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135876
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461582
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727102
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.70
BayesDel_addAF
Uncertain
0.096
D
BayesDel_noAF
Uncertain
0.0
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.43
T;T;D;.;.;T
Eigen
Pathogenic
0.70
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.96
D;D;D;D;D;D
M_CAP
Benign
0.039
D
MetaRNN
Pathogenic
0.79
D;D;D;D;D;D
MetaSVM
Benign
-0.43
T
MutationAssessor
Uncertain
2.9
.;.;M;.;.;.
PrimateAI
Uncertain
0.60
T
PROVEAN
Pathogenic
-6.6
D;D;D;D;D;D
REVEL
Uncertain
0.40
Sift
Uncertain
0.0010
D;D;D;D;D;D
Sift4G
Pathogenic
0.0010
D;D;D;D;D;D
Polyphen
0.98
D;.;D;.;.;.
Vest4
0.81
MutPred
0.56
Gain of phosphorylation at D111 (P = 0.0056);Gain of phosphorylation at D111 (P = 0.0056);Gain of phosphorylation at D111 (P = 0.0056);Gain of phosphorylation at D111 (P = 0.0056);Gain of phosphorylation at D111 (P = 0.0056);.;
MVP
0.78
MPC
0.45
ClinPred
0.99
D
GERP RS
3.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.77
gMVP
0.38

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201838047; hg19: chr12-98921715; API