1-154162364-CAAAAAAAAAAAAA-C

Variant names:

• chr1-154162364-CAAAAAAAAAAAAA-C
• rs58289686
• NM_152263.4:c.*5560_*5572delTTTTTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_152263.4(TPM3):​c.*5560_*5572delTTTTTTTTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 0)
• Consequence: TPM3 NM_152263.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.530
• Publications: 1 publications found

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]

TPM3 Gene-Disease associations (from GenCC):

• congenital myopathy 4A, autosomal dominant

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• TPM3-related myopathy

  Inheritance: SD, AD, AR Classification: DEFINITIVE Submitted by: ClinGen
• congenital myopathy 4B, autosomal recessive

  Inheritance: SD, AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
• congenital fiber-type disproportion myopathy

  Inheritance: SD, AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
• cap myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• childhood-onset nemaline myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• congenital generalized hypercontractile muscle stiffness syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• intermediate nemaline myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152263.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPM3	NM_152263.4	MANE Select	c.*5560_*5572delTTTTTTTTTTTTT		3_prime_UTR	Exon 10 of 10	NP_689476.2	P06753-1
	TPM3	NM_001364682.1		c.*5560_*5572delTTTTTTTTTTTTT		3_prime_UTR	Exon 10 of 10	NP_001351611.1	A0A2R2Y2Q3
	TPM3	NM_001364683.1		c.*5560_*5572delTTTTTTTTTTTTT		3_prime_UTR	Exon 9 of 9	NP_001351612.1	P06753-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPM3	ENST00000651641.1	MANE Select	c.*5560_*5572delTTTTTTTTTTTTT		3_prime_UTR	Exon 10 of 10	ENSP00000498577.1	P06753-1
	TPM3	ENST00000330188.13	TSL:1	c.665-4656_665-4644delTTTTTTTTTTTTT		intron	N/A	ENSP00000339035.7	P06753-5
	TPM3	ENST00000368533.8	TSL:1	c.665-4656_665-4644delTTTTTTTTTTTTT		intron	N/A	ENSP00000357521.3	P06753-2

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 1 AN: 75104 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000266

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0000133 AC: 1 AN: 75104 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 34238

African (AFR) AF: 0.00 AC: 0 AN: 20316

American (AMR) AF: 0.00 AC: 0 AN: 6080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2116

East Asian (EAS) AF: 0.00 AC: 0 AN: 3148

South Asian (SAS) AF: 0.00 AC: 0 AN: 2082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 144

European-Non Finnish (NFE) AF: 0.0000266 AC: 1 AN: 37570

Other (OTH) AF: 0.00 AC: 0 AN: 934

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs58289686; hg19: chr1-154134840;