1-154162364-C-CA

Position:

• chr1-154162364-C-CA

Variant summary

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

The NM_152263.4(TPM3):​c.*5572_*5573insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.35 (4909 hom., cov: 0)
• Consequence: TPM3 NM_152263.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• 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.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPM3	NM_152263.4	c.*5572_*5573insT		3_prime_UTR_variant	10/10	ENST00000651641.1	NP_689476.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPM3	ENST00000651641.1	c.*5572_*5573insT		3_prime_UTR_variant	10/10		NM_152263.4	ENSP00000498577	P1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 26261 AN: 74886 Hom.: 4911 Cov.: 0

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.352

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.351 AC: 26246 AN: 74858 Hom.: 4909 Cov.: 0 AF XY: 0.345 AC XY: 11760 AN XY: 34122

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.380

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital myopathy with fiber type disproportion Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Nemaline myopathy Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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;