chr1-154185911-T-C

Position:

• chr1-154185911-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152263.4(TPM3):​c.243+5275A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 150,804 control chromosomes in the GnomAD database, including 31,492 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (31492 hom., cov: 29)
• Consequence: TPM3 NM_152263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPM3	NM_152263.4	c.243+5275A>G		intron_variant		ENST00000651641.1	NP_689476.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPM3	ENST00000651641.1	c.243+5275A>G		intron_variant			NM_152263.4	ENSP00000498577.1
TPM3	ENST00000368530.7	c.243+5275A>G		intron_variant		1		ENSP00000357516.3
TPM3	ENST00000271850.11	c.243+5275A>G		intron_variant		5		ENSP00000271850.7
TPM3	ENST00000651644.1	n.243+5275A>G		intron_variant				ENSP00000498648.1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 95237 AN: 150686 Hom.: 31455 Cov.: 29

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.882

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.632 AC: 95327 AN: 150804 Hom.: 31492 Cov.: 29 AF XY: 0.636 AC XY: 46895 AN XY: 73688

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.883

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.584

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.624

Alfa AF: 0.555 Hom.: 30870

Bravo AF: 0.650

Asia WGS AF: 0.769 AC: 2672 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4845605; hg19: chr1-154158387;