rs751682878
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_003280.3(TNNC1):c.72C>T(p.Phe24=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000466 in 1,460,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000047 ( 0 hom. )
Consequence
TNNC1
NM_003280.3 synonymous
NM_003280.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0650
Genes affected
TNNC1 (HGNC:11943): (troponin C1, slow skeletal and cardiac type) Troponin is a central regulatory protein of striated muscle contraction, and together with tropomyosin, is located on the actin filament. Troponin consists of 3 subunits: TnI, which is the inhibitor of actomyosin ATPase; TnT, which contains the binding site for tropomyosin; and TnC, the protein encoded by this gene. The binding of calcium to TnC abolishes the inhibitory action of TnI, thus allowing the interaction of actin with myosin, the hydrolysis of ATP, and the generation of tension. Mutations in this gene are associated with cardiomyopathy dilated type 1Z. [provided by RefSeq, Oct 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
Variant 3-52452236-G-A is Benign according to our data. Variant chr3-52452236-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 239536.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-52452236-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.065 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0000466 (68/1460522) while in subpopulation NFE AF= 0.0000558 (62/1112002). AF 95% confidence interval is 0.0000444. There are 0 homozygotes in gnomad4_exome. There are 33 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High AC in GnomAdExome4 at 68 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNNC1 | NM_003280.3 | c.72C>T | p.Phe24= | synonymous_variant | 3/6 | ENST00000232975.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNNC1 | ENST00000232975.8 | c.72C>T | p.Phe24= | synonymous_variant | 3/6 | 1 | NM_003280.3 | P1 | |
TNNC1 | ENST00000496590.1 | c.-61C>T | 5_prime_UTR_variant | 2/4 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000280 AC: 7AN: 250338Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135414
GnomAD3 exomes
AF:
AC:
7
AN:
250338
Hom.:
AF XY:
AC XY:
1
AN XY:
135414
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000466 AC: 68AN: 1460522Hom.: 0 Cov.: 31 AF XY: 0.0000454 AC XY: 33AN XY: 726590
GnomAD4 exome
AF:
AC:
68
AN:
1460522
Hom.:
Cov.:
31
AF XY:
AC XY:
33
AN XY:
726590
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
Alfa
AF:
Hom.:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Dilated cardiomyopathy 1Z;C2750472:Hypertrophic cardiomyopathy 13 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Apr 12, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 04, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at