chr15-63042558-A-G
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000893958.1(TPM1):c.-272A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000401 in 249,128 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: 𝑓 0.0 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000040 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TPM1
ENST00000893958.1 5_prime_UTR
ENST00000893958.1 5_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.383
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]
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ACMG classification
Classification was made for transcript
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=-0.39).
Variant Effect in Transcripts
ACMG analysis was done for transcript: ENST00000893958.1. 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.-272A>G | upstream_gene | N/A | NP_001018005.1 | D9YZV4 | ||
| TPM1 | NM_001365778.1 | c.-272A>G | upstream_gene | N/A | NP_001352707.1 | Q6ZN40 | |||
| TPM1 | NM_001407322.1 | c.-272A>G | upstream_gene | N/A | NP_001394251.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TPM1 | ENST00000893958.1 | c.-272A>G | 5_prime_UTR | Exon 1 of 10 | ENSP00000564017.1 | ||||
| TPM1-AS | ENST00000804116.1 | n.122+6007T>C | intron | N/A | |||||
| TPM1-AS | ENST00000804117.1 | n.171+830T>C | intron | N/A |
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 151594Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
0
AN:
151594
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000401 AC: 1AN: 249128Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 136740 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
249128
Hom.:
AF XY:
AC XY:
0
AN XY:
136740
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
4878
American (AMR)
AF:
AC:
0
AN:
11150
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
6220
East Asian (EAS)
AF:
AC:
0
AN:
12236
South Asian (SAS)
AF:
AC:
0
AN:
41802
European-Finnish (FIN)
AF:
AC:
0
AN:
11982
Middle Eastern (MID)
AF:
AC:
0
AN:
990
European-Non Finnish (NFE)
AF:
AC:
1
AN:
146824
Other (OTH)
AF:
AC:
0
AN:
13046
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00 AC: 0AN: 151594Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74060
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
151594
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74060
African (AFR)
AF:
AC:
0
AN:
41242
American (AMR)
AF:
AC:
0
AN:
15244
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5106
South Asian (SAS)
AF:
AC:
0
AN:
4786
European-Finnish (FIN)
AF:
AC:
0
AN:
10542
Middle Eastern (MID)
AF:
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67898
Other (OTH)
AF:
AC:
0
AN:
2088
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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