1-154162364-CAAAAAAAAAAAAA-CAAAAAAAAAA

Variant names:

• chr1-154162364-CAAA-C
• rs58289686
• ENST00000651641:c.*5570_*5572delTTT

Variant summary

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

The NM_152263.4(TPM3):​c.*5570_*5572delTTT 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 0.018 (22 hom., cov: 0)
• Consequence: TPM3 NM_152263.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.530

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 (AFR) allele frequency at 95% confidence interval = 0.062 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPM3	NM_152263.4	c.*5570_*5572delTTT		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.*5570_*5572delTTT		3_prime_UTR_variant	Exon 10 of 10		NM_152263.4	ENSP00000498577.1

Frequencies

GnomAD3 genomes AF: 0.0184 AC: 1382 AN: 75068 Hom.: 22 Cov.: 0

Gnomad AFR AF: 0.0650

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00609

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000953

Gnomad SAS AF: 0.000961

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000240

Gnomad OTH AF: 0.00964

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

GnomAD4 genome AF: 0.0184 AC: 1382 AN: 75040 Hom.: 22 Cov.: 0 AF XY: 0.0191 AC XY: 654 AN XY: 34208

Gnomad4 AFR AF: 0.0649

Gnomad4 AMR AF: 0.00608

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000957

Gnomad4 SAS AF: 0.000968

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.000240

Gnomad4 OTH AF: 0.00957

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;