6-123337680-G-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_006073.4(TRDN):c.1370-11C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,409,608 control chromosomes in the GnomAD database, including 30,454 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.18 ( 3551 hom., cov: 32)
Exomes 𝑓: 0.18 ( 26903 hom. )
Consequence
TRDN
NM_006073.4 splice_polypyrimidine_tract, intron
NM_006073.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.002238
2
Clinical Significance
Conservation
PhyloP100: 0.950
Genes affected
TRDN (HGNC:12261): (triadin) This gene encodes an integral membrane protein found in skeletal and cardiac muscle. The encoded protein plays a role in skeletal muscle excitation-contraction coupling as part of the calcium release complex and is required for normal skeletal muscle strength. This protein indirectly links triads and microtubules in skeletal muscle. Mutations in this gene are associated with cardiac arrythmia syndrome and some variants in this gene may be associated with sudden cardiac death. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 6-123337680-G-T is Benign according to our data. Variant chr6-123337680-G-T is described in ClinVar as [Benign]. Clinvar id is 227111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-123337680-G-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
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TRDN | NM_006073.4 | c.1370-11C>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000334268.9 | |||
LOC105377984 | XR_942947.3 | n.262G>T | non_coding_transcript_exon_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRDN | ENST00000334268.9 | c.1370-11C>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_006073.4 | A2 |
Frequencies
GnomAD3 genomes AF: 0.185 AC: 28076AN: 151812Hom.: 3550 Cov.: 32
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GnomAD3 exomes AF: 0.249 AC: 32103AN: 129056Hom.: 5123 AF XY: 0.256 AC XY: 17534AN XY: 68620
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GnomAD4 exome AF: 0.177 AC: 222199AN: 1257678Hom.: 26903 Cov.: 21 AF XY: 0.183 AC XY: 114115AN XY: 622224
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GnomAD4 genome AF: 0.185 AC: 28091AN: 151930Hom.: 3551 Cov.: 32 AF XY: 0.198 AC XY: 14671AN XY: 74246
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2014 | 1370-11C>A in intron 21 of TRDN: This variant is not expected to have clinical s ignificance because it has been identified in 15.0% (794/5284) of European Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs9401658). - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 09, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 14, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 22, 2016 | 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. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Catecholaminergic polymorphic ventricular tachycardia 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at