rs7754205

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.2051-19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 1,551,200 control chromosomes in the GnomAD database, including 160,242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14141 hom., cov: 31)

Exomes 𝑓: 0.45 ( 146101 hom. )

Consequence

TRDN
NM_006073.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.929

Publications

8 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:

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=-0.92).

BP6

Variant 6-123218759-C-T is Benign according to our data. Variant chr6-123218759-C-T is described in ClinVar as Benign. ClinVar VariationId is 259915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRDN	NM_006073.4 link	c.2051-19G>A		intron_variant	Intron 40 of 40	ENST00000334268.9	NP_006064.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRDN	ENST00000334268.9 link	c.2051-19G>A		intron_variant	Intron 40 of 40	1	NM_006073.4	ENSP00000333984.5

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64429

AN:

151440

Hom.:

14120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.349

Gnomad AMI

AF:

0.427

Gnomad AMR

AF:

0.551

Gnomad ASJ

AF:

0.503

Gnomad EAS

AF:

0.317

Gnomad SAS

AF:

0.288

Gnomad FIN

AF:

0.353

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.467

Gnomad OTH

AF:

0.485

GnomAD2 exomes

AF:

0.442

AC:

71937

AN:

162720

AF XY:

0.431

show subpopulations

Gnomad AFR exome

AF:

0.358

Gnomad AMR exome

AF:

0.621

Gnomad ASJ exome

AF:

0.500

Gnomad EAS exome

AF:

0.301

Gnomad FIN exome

AF:

0.360

Gnomad NFE exome

AF:

0.475

Gnomad OTH exome

AF:

0.476

GnomAD4 exome

AF:

0.453

AC:

633567

AN:

1399642

Hom.:

146101

Cov.:

AF XY:

0.447

AC XY:

308699

AN XY:

690788

show subpopulations

African (AFR)

AF:

0.353

AC:

11214

AN:

31728

American (AMR)

AF:

0.613

AC:

21896

AN:

35722

Ashkenazi Jewish (ASJ)

AF:

0.501

AC:

12524

AN:

24990

East Asian (EAS)

AF:

0.312

AC:

11315

AN:

36278

South Asian (SAS)

AF:

0.294

AC:

23419

AN:

79616

European-Finnish (FIN)

AF:

0.360

AC:

17985

AN:

49890

Middle Eastern (MID)

AF:

0.514

AC:

2912

AN:

5662

European-Non Finnish (NFE)

AF:

0.470

AC:

506320

AN:

1077676

Other (OTH)

AF:

0.447

AC:

25982

AN:

58080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

15068

30137

45205

60274

75342

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15176

30352

45528

60704

75880

<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:

0.426

AC:

64500

AN:

151558

Hom.:

14141

Cov.:

AF XY:

0.420

AC XY:

31110

AN XY:

74044

show subpopulations

African (AFR)

AF:

0.349

AC:

14427

AN:

41350

American (AMR)

AF:

0.552

AC:

8383

AN:

15186

Ashkenazi Jewish (ASJ)

AF:

0.503

AC:

1745

AN:

3466

East Asian (EAS)

AF:

0.317

AC:

1613

AN:

5086

South Asian (SAS)

AF:

0.287

AC:

1384

AN:

4814

European-Finnish (FIN)

AF:

0.353

AC:

3727

AN:

10560

Middle Eastern (MID)

AF:

0.551

AC:

162

AN:

294

European-Non Finnish (NFE)

AF:

0.467

AC:

31636

AN:

67784

Other (OTH)

AF:

0.491

AC:

1034

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1839

3678

5518

7357

9196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

590

1180

1770

2360

2950

<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:

0.456

Hom.:

3966

Bravo

AF:

0.444

Asia WGS

AF:

0.351

AC:

1220

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Jul 08, 2021

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 21, 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. -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

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

-0.92

CADD

Benign

0.083

(source)

DANN

Benign

0.25

PhyloP100

-0.93

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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