rs910746839
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001032283.3(TMPO):āc.213C>Gā(p.Arg71=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 1,600,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 33)
Exomes š: 0.0000090 ( 0 hom. )
Consequence
TMPO
NM_001032283.3 synonymous
NM_001032283.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.22
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 Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
Variant 12-98516080-C-G is Benign according to our data. Variant chr12-98516080-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 469132.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.22 with no splicing effect.
BS2
?
High AC in GnomAdExome4 at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMPO | NM_001032283.3 | c.213C>G | p.Arg71= | synonymous_variant | 1/9 | ENST00000556029.6 | |
TMPO-AS1 | NR_027157.1 | n.147G>C | non_coding_transcript_exon_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMPO | ENST00000556029.6 | c.213C>G | p.Arg71= | synonymous_variant | 1/9 | 1 | NM_001032283.3 | ||
TMPO-AS1 | ENST00000548760.2 | n.343G>C | non_coding_transcript_exon_variant | 1/2 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152138Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000942 AC: 2AN: 212416Hom.: 0 AF XY: 0.00000843 AC XY: 1AN XY: 118630
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GnomAD4 exome AF: 0.00000898 AC: 13AN: 1448122Hom.: 0 Cov.: 31 AF XY: 0.00000833 AC XY: 6AN XY: 720004
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152250Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74428
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 27, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Loeys-Dietz syndrome 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 08, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 04, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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