1-154162081-A-C

Position:

• chr1-154162081-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152263.4(TPM3):​c.*5856T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,026 control chromosomes in the GnomAD database, including 7,827 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (7827 hom., cov: 30)
• Consequence: TPM3 NM_152263.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.369

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-154162081-A-C is Benign according to our data. Variant chr1-154162081-A-C is described in ClinVar as [Benign]. Clinvar id is 292625.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPM3	NM_152263.4	c.*5856T>G		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.*5856T>G		3_prime_UTR_variant	10/10		NM_152263.4	ENSP00000498577	P1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45929 AN: 151908 Hom.: 7823 Cov.: 30

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.302 AC: 45950 AN: 152026 Hom.: 7827 Cov.: 30 AF XY: 0.308 AC XY: 22909 AN XY: 74308

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.341

Alfa AF: 0.338 Hom.: 3369

Bravo AF: 0.308

Asia WGS AF: 0.387 AC: 1345 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital myopathy with fiber type disproportion Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Nemaline myopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3196889; hg19: chr1-154134557;