6-123337680-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

catecholaminergic polymorphic ventricular tachycardia
Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
catecholaminergic polymorphic ventricular tachycardia 5
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
familial long QT syndrome
Inheritance: AR Classification: STRONG Submitted by: G2P
long QT syndrome
Inheritance: AR Classification: STRONG Submitted by: ClinGen

TRDN links:

LOC105377984 (HGNC:):

LOC105377984 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 227111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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
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

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

GnomAD2 exomes

AF:

0.249

AC:

32103

AN:

129056

AF XY:

0.256

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 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

African (AFR)

AF:

0.0678

AC:

1858

AN:

27406

American (AMR)

AF:

0.263

AC:

6861

AN:

26088

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

4234

AN:

22976

East Asian (EAS)

AF:

0.657

AC:

20576

AN:

31326

South Asian (SAS)

AF:

0.366

AC:

24316

AN:

66438

European-Finnish (FIN)

AF:

0.245

AC:

11319

AN:

46112

Middle Eastern (MID)

AF:

0.226

AC:

1185

AN:

5254

European-Non Finnish (NFE)

AF:

0.145

AC:

142539

AN:

980182

Other (OTH)

AF:

0.179

AC:

9311

AN:

51896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.412

Heterozygous variant carriers

6083

12165

18248

24330

30413

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5016

10032

15048

20064

25080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.185

AC:

28091

AN:

151930

Hom.:

3551

Cov.:

AF XY:

0.198

AC XY:

14671

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.0847

AC:

3516

AN:

41488

American (AMR)

AF:

0.215

AC:

3280

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.194

AC:

673

AN:

3466

East Asian (EAS)

AF:

0.630

AC:

3246

AN:

5150

South Asian (SAS)

AF:

0.413

AC:

1988

AN:

4818

European-Finnish (FIN)

AF:

0.275

AC:

2897

AN:

10526

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.176

AC:

11951

AN:

67940

Other (OTH)

AF:

0.168

AC:

353

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1074

2149

3223

4298

5372

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

PreventionGenetics, part of Exact Sciences

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.

Oct 14, 2016

Eurofins Ntd Llc (ga)

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

(source)

DANN

Benign

0.57

PhyloP100

0.95

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over