15-63043765-C-T

Variant names:

• chr15-63043765-C-T
• rs74573041
• ENST00000267996.11:c.174C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The ENST00000267996.11(TPM1):​c.174C>T​(p.Asp58Asp) variant causes a synonymous change. The variant allele was found at a frequency of 0.000179 in 1,549,958 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00074 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: TPM1 ENST00000267996.11 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 3.78
• 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: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 15-63043765-C-T is Benign according to our data. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043765-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000742 (113/152322) while in subpopulation AFR AF = 0.00255 (106/41574). AF 95% confidence interval is 0.00216. There are 0 homozygotes in GnomAd4. There are 57 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 113 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPM1	NM_001018005.2	c.115-262C>T		intron_variant	Intron 1 of 9	ENST00000403994.9	NP_001018005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPM1	ENST00000403994.9	c.115-262C>T		intron_variant	Intron 1 of 9	1	NM_001018005.2	ENSP00000385107.4

Frequencies

GnomAD3 genomes AF: 0.000742 AC: 113 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00256

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000210 AC: 31 AN: 147278 AF XY: 0.000192

Gnomad AFR exome AF: 0.00258

Gnomad AMR exome AF: 0.000163

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000369

Gnomad OTH exome AF: 0.000941

GnomAD4 exome AF: 0.000118 AC: 165 AN: 1397636 Hom.: 1 Cov.: 31 AF XY: 0.000122 AC XY: 84 AN XY: 689446

African (AFR) AF: 0.00357 AC: 113 AN: 31634

American (AMR) AF: 0.000252 AC: 9 AN: 35734

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25166

East Asian (EAS) AF: 0.00 AC: 0 AN: 35854

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79268

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47406

Middle Eastern (MID) AF: 0.00125 AC: 7 AN: 5582

European-Non Finnish (NFE) AF: 0.0000139 AC: 15 AN: 1079016

Other (OTH) AF: 0.000345 AC: 20 AN: 57976

GnomAD4 genome AF: 0.000742 AC: 113 AN: 152322 Hom.: 0 Cov.: 32 AF XY: 0.000765 AC XY: 57 AN XY: 74480

African (AFR) AF: 0.00255 AC: 106 AN: 41574

American (AMR) AF: 0.000327 AC: 5 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000469 Hom.: 0

Bravo AF: 0.000929

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 08, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Asp58Asp in exon 1A of TPM1: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 0.2% (37/15892) of African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.b roadinstitute.org; dbSNP rs74573041) BA1, BP4, BP7 -

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

BS1;BP6;BP7 -

not provided Benign:3

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TPM1: BP4, BS1 -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Cardiomyopathy Benign:1

Oct 15, 2018

Color Diagnostics, LLC DBA Color Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Benign	0.97
PhyloP100		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=77/23	polymorphism

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: rs74573041; hg19: chr15-63335964;