rs727503491
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM4_SupportingBS2
The ENST00000266732.8(TMPO):βc.2042_2044delβ(p.Gly681del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000279 in 1,613,252 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ).
Frequency
Genomes: π 0.000013 ( 0 hom., cov: 33)
Exomes π: 0.000029 ( 0 hom. )
Consequence
TMPO
ENST00000266732.8 inframe_deletion
ENST00000266732.8 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.51
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in ENST00000266732.8. Strenght limited to Supporting due to length of the change: 1aa.
BS2
?
High AC in GnomAdExome4 at 43 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMPO | NM_001032283.3 | c.565+2461_565+2463del | intron_variant | ENST00000556029.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMPO | ENST00000556029.6 | c.565+2461_565+2463del | intron_variant | 1 | NM_001032283.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152204Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000320 AC: 8AN: 249992Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135330
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GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461048Hom.: 0 AF XY: 0.0000371 AC XY: 27AN XY: 726872
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74358
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 16, 2014 | The p.Gly681del variant in TMPO has not been previously reported in any other fa milies with cardiomyopathy. Data from large population studies is insufficient t o assess the frequency of this variant. This variant is a deletion of a single a mino acid at position 681 and is not predicted to alter the protein reading-fram e. It is unclear if this deletion will impact the protein. In summary, the clini cal significance of the p.Gly681del variant is uncertain. - |
Loeys-Dietz syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2023 | This variant, c.2042_2044del, results in the deletion of 1 amino acid(s) of the TMPO protein (p.Gly681del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs753373682, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with TMPO-related conditions. ClinVar contains an entry for this variant (Variation ID: 165472). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
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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