Genetic Variant NM_006073.4:c.2051-19G>A (chr6-123218759-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -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

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:

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=-0.92).

BP6

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

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	Q13061-1

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		Q13061-1

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

GnomAD3 exomes

AF:

0.442

AC:

71937

AN:

162720

Hom.:

16833

AF XY:

0.431

AC XY:

36795

AN XY:

85398

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 SAS exome

AF:

0.295

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

Gnomad4 AFR exome

AF:

0.353

Gnomad4 AMR exome

AF:

0.613

Gnomad4 ASJ exome

AF:

0.501

Gnomad4 EAS exome

AF:

0.312

Gnomad4 SAS exome

AF:

0.294

Gnomad4 FIN exome

AF:

0.360

Gnomad4 NFE exome

AF:

0.470

Gnomad4 OTH exome

AF:

0.447

GnomAD4 genome

AF:

0.426

AC:

64500

AN:

151558

Hom.:

14141

Cov.:

AF XY:

0.420

AC XY:

31110

AN XY:

74044

show subpopulations

Gnomad4 AFR

AF:

0.349

Gnomad4 AMR

AF:

0.552

Gnomad4 ASJ

AF:

0.503

Gnomad4 EAS

AF:

0.317

Gnomad4 SAS

AF:

0.287

Gnomad4 FIN

AF:

0.353

Gnomad4 NFE

AF:

0.467

Gnomad4 OTH

AF:

0.491

Alfa

AF:

0.458

Hom.:

3914

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

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

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

- -

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

- -

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. -

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

DANN

Benign

0.25

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

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