rs727503495
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_003280.3(TNNC1):c.56-8G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000317 in 1,609,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_003280.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNNC1 | NM_003280.3 | c.56-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000232975.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNNC1 | ENST00000232975.8 | c.56-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_003280.3 | P1 | |||
TNNC1 | ENST00000496590.1 | c.-77-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152180Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000162 AC: 4AN: 247536Hom.: 0 AF XY: 0.00000745 AC XY: 1AN XY: 134188
GnomAD4 exome AF: 0.0000329 AC: 48AN: 1456830Hom.: 0 Cov.: 31 AF XY: 0.0000331 AC XY: 24AN XY: 724904
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152180Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74342
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 04, 2014 | Variant classified as Uncertain Significance - Favor Benign. The 56-8G>A variant in TNNC1 has not been reported in individuals with cardiomyopathy or in large p opulation studies. This variant is located in the 3' splice region. Computationa l tools do not suggest an impact to splicing. However, this information is not p redictive enough to rule out pathogenicity. Additional information is needed to fully assess the clinical significance of the 56-8G>A variant. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | TNNC1: PM2, BP4 - |
Dilated cardiomyopathy 1Z;C2750472:Hypertrophic cardiomyopathy 13 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 24, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at