15-63042705-C-T

Variant names:

• chr15-63042705-C-T
• rs957045052
• ENST00000288398.10:c.-125C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000288398.10(TPM1):​c.-125C>T variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00000169 in 593,418 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: TPM1 ENST00000288398.10 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.37
• Publications: 0 publications found

Genes affected

TPM1 (HGNC:12010): (tropomyosin 1) This gene is a member of the tropomyosin family of highly conserved, widely distributed actin-binding proteins involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells. Tropomyosin is composed of two alpha-helical chains arranged as a coiled-coil. It is polymerized end to end along the two grooves of actin filaments and provides stability to the filaments. The encoded protein is one type of alpha helical chain that forms the predominant tropomyosin of striated muscle, where it also functions in association with the troponin complex to regulate the calcium-dependent interaction of actin and myosin during muscle contraction. In smooth muscle and non-muscle cells, alternatively spliced transcript variants encoding a range of isoforms have been described. Mutations in this gene are associated with type 3 familial hypertrophic cardiomyopathy and dilated cardiomyopathy 1Y. [provided by RefSeq, Jun 2022]

TPM1-AS (HGNC:53635): (TPM1 antisense RNA)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000288398.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPM1	NM_001018005.2	MANE Select	c.-125C>T		upstream_gene	N/A	NP_001018005.1	D9YZV4
	TPM1	NM_001365778.1		c.-125C>T		upstream_gene	N/A	NP_001352707.1	Q6ZN40
	TPM1	NM_001407322.1		c.-125C>T		upstream_gene	N/A	NP_001394251.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPM1	ENST00000288398.10	TSL:1	c.-125C>T		5_prime_UTR	Exon 1 of 10	ENSP00000288398.6	P09493-10
	TPM1	ENST00000358278.7	TSL:1	c.-125C>T		5_prime_UTR	Exon 1 of 9	ENSP00000351022.3	P09493-3
	TPM1	ENST00000893959.1		c.-125C>T		5_prime_UTR	Exon 1 of 10	ENSP00000564018.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000169 AC: 1 AN: 593418 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 316698

African (AFR) AF: 0.00 AC: 0 AN: 15154

American (AMR) AF: 0.0000358 AC: 1 AN: 27954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17276

East Asian (EAS) AF: 0.00 AC: 0 AN: 32074

South Asian (SAS) AF: 0.00 AC: 0 AN: 57236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46052

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2538

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 364126

Other (OTH) AF: 0.00 AC: 0 AN: 31008

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Benign	0.97
PhyloP100		5.4
PromoterAI		0.17	Neutral

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

Other links and lift over

dbSNP: rs957045052; hg19: chr15-63334904;