1-154162364-CAAAAAAAAAAAAA-CAAAAAAAAAAAAAAA

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_152263.4(TPM3):​c.*5571_*5572dupTT 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 0.019 (38 hom., cov: 0)
• Consequence: TPM3 NM_152263.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.459

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.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0189 (1413/74740) while in subpopulation EAS AF= 0.0313 (98/3132). AF 95% confidence interval is 0.0263. There are 38 homozygotes in gnomad4. There are 622 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 38 SD gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 1415 AN: 74766 Hom.: 38 Cov.: 0

Gnomad AFR AF: 0.0159

Gnomad AMI AF: 0.00422

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.0315

Gnomad SAS AF: 0.00481

Gnomad FIN AF: 0.0184

Gnomad MID AF: 0.0417

Gnomad NFE AF: 0.0217

Gnomad OTH AF: 0.0268

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

GnomAD4 genome AF: 0.0189 AC: 1413 AN: 74740 Hom.: 38 Cov.: 0 AF XY: 0.0182 AC XY: 622 AN XY: 34098

Gnomad4 AFR AF: 0.0159

Gnomad4 AMR AF: 0.0112

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.0313

Gnomad4 SAS AF: 0.00484

Gnomad4 FIN AF: 0.0184

Gnomad4 NFE AF: 0.0217

Gnomad4 OTH AF: 0.0267

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;