6-123337680-G-T

Variant names:

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 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 intron

Scores

Splicing: ADA: 0.002238

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.950

Variant links:

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]

TRDN links:

LOC105377984 (HGNC:):

LOC105377984 links:

Genome browser will be placed here

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 rank	MANE	Protein	UniProt
TRDN	NM_006073.4 link	c.1370-11C>A		intron_variant	Intron 21 of 40	ENST00000334268.9	NP_006064.2	Q13061-1
LOC105377984	XR_942947.3 link	n.262G>T		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRDN	ENST00000334268.9 link	c.1370-11C>A		intron_variant	Intron 21 of 40	1	NM_006073.4	ENSP00000333984.5		Q13061-1

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28076

AN:

151812

Hom.:

3550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0845

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.194

Gnomad EAS

AF:

0.630

Gnomad SAS

AF:

0.412

Gnomad FIN

AF:

0.275

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.176

Gnomad OTH

AF:

0.171

GnomAD3 exomes

AF:

0.249

AC:

32103

AN:

129056

Hom.:

5123

AF XY:

0.256

AC XY:

17534

AN XY:

68620

show subpopulations

Gnomad AFR exome

AF:

0.0807

Gnomad AMR exome

AF:

0.278

Gnomad ASJ exome

AF:

0.200

Gnomad EAS exome

AF:

0.607

Gnomad SAS exome

AF:

0.381

Gnomad FIN exome

AF:

0.270

Gnomad NFE exome

AF:

0.168

Gnomad OTH exome

AF:

0.215

GnomAD4 exome

AF:

0.177

AC:

222199

AN:

1257678

Hom.:

26903

Cov.:

AF XY:

0.183

AC XY:

114115

AN XY:

622224

show subpopulations

Gnomad4 AFR exome

AF:

0.0678

Gnomad4 AMR exome

AF:

0.263

Gnomad4 ASJ exome

AF:

0.184

Gnomad4 EAS exome

AF:

0.657

Gnomad4 SAS exome

AF:

0.366

Gnomad4 FIN exome

AF:

0.245

Gnomad4 NFE exome

AF:

0.145

Gnomad4 OTH exome

AF:

0.179

GnomAD4 genome

AF:

0.185

AC:

28091

AN:

151930

Hom.:

3551

Cov.:

AF XY:

0.198

AC XY:

14671

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.0847

Gnomad4 AMR

AF:

0.215

Gnomad4 ASJ

AF:

0.194

Gnomad4 EAS

AF:

0.630

Gnomad4 SAS

AF:

0.413

Gnomad4 FIN

AF:

0.275

Gnomad4 NFE

AF:

0.176

Gnomad4 OTH

AF:

0.168

Alfa

AF:

0.136

Hom.:

375

Bravo

AF:

0.174

Asia WGS

AF:

0.411

AC:

1420

AN:

3464

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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). -

Apr 09, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 14, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 22, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Catecholaminergic polymorphic ventricular tachycardia 1

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Catecholaminergic polymorphic ventricular tachycardia 5

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0022

dbscSNV1_RF

Benign

0.21

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over