chr1-154158721-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The ENST00000368531.6(TPM3):c.*248C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0437 in 495,356 control chromosomes in the GnomAD database, including 593 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.038 ( 154 hom., cov: 32)
Exomes 𝑓: 0.046 ( 439 hom. )
Consequence
TPM3
ENST00000368531.6 3_prime_UTR
ENST00000368531.6 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.788
Genes affected
TPM3 (HGNC:12012): (tropomyosin 3) This gene encodes a member of the tropomyosin family of actin-binding proteins. Tropomyosins are dimers of coiled-coil proteins that provide stability to actin filaments and regulate access of other actin-binding proteins. Mutations in this gene result in autosomal dominant nemaline myopathy and other muscle disorders. This locus is involved in translocations with other loci, including anaplastic lymphoma receptor tyrosine kinase (ALK) and neurotrophic tyrosine kinase receptor type 1 (NTRK1), which result in the formation of fusion proteins that act as oncogenes. There are numerous pseudogenes for this gene on different chromosomes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant 1-154158721-G-A is Benign according to our data. Variant chr1-154158721-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1198687.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0513 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPM3 | NM_001043352.2 | c.*248C>T | 3_prime_UTR_variant | 8/8 | |||
TPM3 | NM_001043353.2 | c.*248C>T | 3_prime_UTR_variant | 8/8 | |||
TPM3 | NM_001364681.2 | c.*248C>T | 3_prime_UTR_variant | 9/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPM3 | ENST00000368531.6 | c.*248C>T | 3_prime_UTR_variant | 8/8 | 1 | ||||
TPM3 | ENST00000330188.13 | c.665-1000C>T | intron_variant | 1 | |||||
TPM3 | ENST00000368533.8 | c.665-1000C>T | intron_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0382 AC: 5807AN: 152136Hom.: 155 Cov.: 32
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GnomAD4 exome AF: 0.0462 AC: 15861AN: 343102Hom.: 439 Cov.: 0 AF XY: 0.0473 AC XY: 8547AN XY: 180518
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GnomAD4 genome ? AF: 0.0381 AC: 5803AN: 152254Hom.: 154 Cov.: 32 AF XY: 0.0376 AC XY: 2800AN XY: 74436
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at