rs79182520

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006073.4(TRDN):c.430C>T(p.His144Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 1,240,332 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 23 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 80 hom. )

Consequence

TRDN
NM_006073.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 2.75

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:

ENSG00000285691 (HGNC:):

ENSG00000285691 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 (MetaRNN=0.0015872121).

BP6

Variant 6-123530560-G-A is Benign according to our data. Variant chr6-123530560-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 227121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-123530560-G-A is described in Lovd as [Benign]. Variant chr6-123530560-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRDN	NM_006073.4 link	c.430C>T	p.His144Tyr	missense_variant	Exon 5 of 41	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.430C>T	p.His144Tyr	missense_variant	Exon 5 of 41	1	NM_006073.4	ENSP00000333984.5		Q13061-1

Frequencies

GnomAD3 genomes

AF:

0.00345

AC:

523

AN:

151532

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000920

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0917

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000737

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.00391

AC:

343

AN:

87800

Hom.:

AF XY:

0.00355

AC XY:

170

AN XY:

47916

show subpopulations

Gnomad AFR exome

AF:

0.000271

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0704

Gnomad SAS exome

AF:

0.00137

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000813

Gnomad OTH exome

AF:

0.00231

GnomAD4 exome

AF:

0.00209

AC:

2275

AN:

1088676

Hom.:

Cov.:

AF XY:

0.00204

AC XY:

1098

AN XY:

537104

show subpopulations

Gnomad4 AFR exome

AF:

0.000182

Gnomad4 AMR exome

AF:

0.0000645

Gnomad4 ASJ exome

AF:

0.0000512

Gnomad4 EAS exome

AF:

0.0731

Gnomad4 SAS exome

AF:

0.00196

Gnomad4 FIN exome

AF:

0.0000255

Gnomad4 NFE exome

AF:

0.0000442

Gnomad4 OTH exome

AF:

0.00331

GnomAD4 genome

AF:

0.00344

AC:

521

AN:

151656

Hom.:

Cov.:

AF XY:

0.00393

AC XY:

291

AN XY:

74092

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000919

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0916

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000738

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.000409

Hom.:

Bravo

AF:

0.00409

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00334

AC:

Asia WGS

AF:

0.0390

AC:

132

AN:

3414

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Oct 29, 2023

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

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

His144Tyr in exon 5 of TRDN: This variant is not expected to have clinical signi ficance because it has been identified in 11.2% (20/178) of Japanese chromosomes from a broad population by the 1000 Genomes Project (http://www.ncbi.nlm.nih.go v/projects/SNP; dbSNP rs79182520). -

Oct 12, 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

- -

TRDN-related disorder

Benign:1

Apr 09, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Catecholaminergic polymorphic ventricular tachycardia 1

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype

Benign:1

Feb 01, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Catecholaminergic polymorphic ventricular tachycardia 5

Benign:1

Nov 09, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.34

T;.;.;.

Eigen

Benign

-0.0097

Eigen_PC

Benign

0.067

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.85

D;D;D;T

MetaRNN

Benign

0.0016

T;T;T;T

MetaSVM

Benign

-0.50

MutationAssessor

Uncertain

2.3

M;M;.;M

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.8

N;.;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0050

D;.;D;D

Sift4G

Uncertain

0.024

D;D;D;T

Polyphen

0.91

P;.;.;.

Vest4

0.15

MVP

0.47

ClinPred

0.023

GERP RS

5.2

Varity_R

0.16

gMVP

0.037

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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