rs775274966
Positions:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_001276345.2(TNNT2):c.459G>A(p.Glu153=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,996 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: 0.0000055 ( 0 hom. )
Consequence
TNNT2
NM_001276345.2 synonymous
NM_001276345.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.58
Genes affected
TNNT2 (HGNC:11949): (troponin T2, cardiac type) This gene encodes the cardiac isoform of troponin T. The encoded protein is the tropomyosin-binding subunit of the troponin complex, which is located on the thin filament of striated muscles and regulates muscle contraction in response to alterations in intracellular calcium ion concentration. Mutations in this gene have been associated with familial hypertrophic cardiomyopathy as well as with dilated cardiomyopathy. [provided by RefSeq, May 2022]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
?
Variant 1-201364328-C-T is Benign according to our data. Variant chr1-201364328-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 469523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-201364328-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=2.58 with no splicing effect.
BS2
?
High AC in GnomAdExome4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNNT2 | NM_001276345.2 | c.459G>A | p.Glu153= | synonymous_variant | 11/17 | ENST00000656932.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNNT2 | ENST00000656932.1 | c.459G>A | p.Glu153= | synonymous_variant | 11/17 | NM_001276345.2 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250080Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135324
GnomAD3 exomes
AF:
AC:
3
AN:
250080
Hom.:
AF XY:
AC XY:
0
AN XY:
135324
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: 0.00000548 AC: 8AN: 1460996Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726792
GnomAD4 exome
AF:
AC:
8
AN:
1460996
Hom.:
Cov.:
31
AF XY:
AC XY:
3
AN XY:
726792
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
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Dilated cardiomyopathy 1D Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 17, 2020 | - - |
Cardiomyopathy, familial restrictive, 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Hypertrophic cardiomyopathy 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Dilated cardiomyopathy 1D;C1861864:Hypertrophic cardiomyopathy 2;C2676271:Cardiomyopathy, familial restrictive, 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Apr 24, 2023 | - - |
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