rs765923858
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_152263.4(TPM3):c.144G>A(p.Gln48=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,614,042 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 (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
TPM3
NM_152263.4 synonymous
NM_152263.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.28
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 Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
?
Variant 1-154191285-C-T is Benign according to our data. Variant chr1-154191285-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 531181.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=2.28 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPM3 | NM_152263.4 | c.144G>A | p.Gln48= | synonymous_variant | 2/10 | ENST00000651641.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPM3 | ENST00000651641.1 | c.144G>A | p.Gln48= | synonymous_variant | 2/10 | NM_152263.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152210Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000599 AC: 15AN: 250526Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135772
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GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461832Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 727216
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74366
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Congenital myopathy with fiber type disproportion;C5829889:Congenital myopathy 4B, autosomal recessive Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 26, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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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