chr1-154162364-CAA-C

Variant names:

• chr1-154162364-CAA-C
• rs58289686
• ENST00000651641:c.*5571_*5572delTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_152263.4(TPM3):​c.*5571_*5572delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (581 hom., cov: 0)
• Consequence: TPM3 NM_152263.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPM3	NM_152263.4	c.*5571_*5572delTT		3_prime_UTR_variant	Exon 10 of 10	ENST00000651641.1	NP_689476.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPM3	ENST00000651641	c.*5571_*5572delTT		3_prime_UTR_variant	Exon 10 of 10		NM_152263.4	ENSP00000498577.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 13083 AN: 74550 Hom.: 583 Cov.: 0

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0944

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.176

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.175 AC: 13071 AN: 74522 Hom.: 581 Cov.: 0 AF XY: 0.178 AC XY: 6035 AN XY: 33996

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.0944

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.169

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58289686; hg19: chr1-154134840;