NM_001276345.2:c.412-94delC
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_001276345.2(TNNT2):c.412-94delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00946 in 1,303,710 control chromosomes in the GnomAD database, including 95 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001276345.2 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00828 AC: 1260AN: 152218Hom.: 9 Cov.: 33
GnomAD4 exome AF: 0.00962 AC: 11079AN: 1151374Hom.: 86 AF XY: 0.00925 AC XY: 5374AN XY: 581196
GnomAD4 genome AF: 0.00827 AC: 1260AN: 152336Hom.: 9 Cov.: 33 AF XY: 0.00854 AC XY: 636AN XY: 74496
ClinVar
Submissions by phenotype
not provided Benign:2
Variant summary: The TNNT2 c.382-94delC variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 337/30938 control chromosomes at a frequency of 0.0108928, which is approximately 44 times the estimated maximal expected allele frequency of a pathogenic TNNT2 variant (0.00025), suggesting this variant is likely a benign polymorphism. This variant was reported in HCM patients without strong evidence for causality (Erdmann_CG_2003, Jaaskelainen_AM_2004). The variant of interest has not, to our knowledge, been reported by reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Due to the high frequency of this variant in the general population, the lack of impact on protein structure, and the lack of predicted impact on splicing, this variant has been classified as benign. -
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Dilated cardiomyopathy 1D Benign:1
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Cardiomyopathy, familial restrictive, 3 Benign:1
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Hypertrophic cardiomyopathy 2 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at