1-154162364-CAAAAAAAAAAAAA-CAAAAAAAAAAAAAAAA

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_152263.4(TPM3):​c.*5570_*5572dupTTT 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 0.00064 (0 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 Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000642 (48/74780) while in subpopulation SAS AF= 0.000968 (2/2066). AF 95% confidence interval is 0.00042. There are 0 homozygotes in gnomad4. There are 18 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.000628 AC: 47 AN: 74808 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000493

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000495

Gnomad ASJ AF: 0.00333

Gnomad EAS AF: 0.000319

Gnomad SAS AF: 0.000961

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000615

Gnomad OTH AF: 0.00108

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

GnomAD4 genome AF: 0.000642 AC: 48 AN: 74780 Hom.: 0 Cov.: 0 AF XY: 0.000528 AC XY: 18 AN XY: 34092

Gnomad4 AFR AF: 0.000542

Gnomad4 AMR AF: 0.000495

Gnomad4 ASJ AF: 0.00333

Gnomad4 EAS AF: 0.000321

Gnomad4 SAS AF: 0.000968

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000616

Gnomad4 OTH AF: 0.00108

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;