6-123393619-C-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.1105+5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 1,599,324 control chromosomes in the GnomAD database, including 1,732 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 122 hom., cov: 32)

Exomes 𝑓: 0.045 ( 1610 hom. )

Consequence

TRDN
NM_006073.4 splice_region, intron

Scores

Splicing: ADA: 0.4824

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.0620

Publications

3 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 links:

TRDN-AS1 (HGNC:40592): (TRDN antisense RNA 1)

TRDN-AS1 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=-0.47).

BP6

Variant 6-123393619-C-T is Benign according to our data. Variant chr6-123393619-C-T is described in ClinVar as Benign. ClinVar VariationId is 227105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.052 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TRDN	NM_006073.4 link	c.1105+5G>A	splice_region_variant, intron_variant	Intron 13 of 40	ENST00000334268.9	NP_006064.2	Q13061-1
TRDN	NM_001251987.2 link	c.1108+5G>A	splice_region_variant, intron_variant	Intron 13 of 20		NP_001238916.1	A0A590UJV0Q8IVK2
TRDN	NM_001407315.1 link	c.1048+5G>A	splice_region_variant, intron_variant	Intron 12 of 19		NP_001394244.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRDN	ENST00000334268.9 link	c.1105+5G>A	splice_region_variant, intron_variant	Intron 13 of 40	1	NM_006073.4	ENSP00000333984.5	Q13061-1
TRDN	ENST00000662930.1 link	c.1108+5G>A	splice_region_variant, intron_variant	Intron 13 of 20			ENSP00000499585.1	A0A590UJV0
TRDN-AS1	ENST00000587106.6 link	n.55+4144C>T	intron_variant	Intron 1 of 8	5

Frequencies

GnomAD3 genomes

AF:

0.0320

AC:

4860

AN:

151918

Hom.:

122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00967

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.0269

Gnomad ASJ

AF:

0.0208

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00850

Gnomad FIN

AF:

0.0290

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0512

Gnomad OTH

AF:

0.0354

GnomAD2 exomes

AF:

0.0317

AC:

7284

AN:

229690

AF XY:

0.0320

show subpopulations

Gnomad AFR exome

AF:

0.00666

Gnomad AMR exome

AF:

0.0226

Gnomad ASJ exome

AF:

0.0198

Gnomad EAS exome

AF:

0.000117

Gnomad FIN exome

AF:

0.0315

Gnomad NFE exome

AF:

0.0499

Gnomad OTH exome

AF:

0.0374

GnomAD4 exome

AF:

0.0448

AC:

64862

AN:

1447288

Hom.:

1610

Cov.:

AF XY:

0.0438

AC XY:

31493

AN XY:

718744

show subpopulations

African (AFR)

AF:

0.00724

AC:

240

AN:

33168

American (AMR)

AF:

0.0250

AC:

1077

AN:

43160

Ashkenazi Jewish (ASJ)

AF:

0.0197

AC:

505

AN:

25652

East Asian (EAS)

AF:

0.000101

AC:

AN:

39502

South Asian (SAS)

AF:

0.0118

AC:

988

AN:

84008

European-Finnish (FIN)

AF:

0.0320

AC:

1684

AN:

52564

Middle Eastern (MID)

AF:

0.0351

AC:

201

AN:

5730

European-Non Finnish (NFE)

AF:

0.0524

AC:

57833

AN:

1103842

Other (OTH)

AF:

0.0391

AC:

2330

AN:

59662

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

2718

5436

8155

10873

13591

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2092

4184

6276

8368

10460

<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:

0.0320

AC:

4862

AN:

152036

Hom.:

122

Cov.:

AF XY:

0.0295

AC XY:

2190

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.00967

AC:

401

AN:

41486

American (AMR)

AF:

0.0269

AC:

411

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.0208

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.00850

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0290

AC:

307

AN:

10586

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0512

AC:

3477

AN:

67918

Other (OTH)

AF:

0.0350

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

248

496

743

991

1239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0431

Hom.:

331

Bravo

AF:

0.0316

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 03, 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. -

Apr 04, 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

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

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

1105+5G>A in intron 13 of TRDN: This variant is not expected to have clinical si gnificance because it has been identified in 4.8% (393/8134) of European America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs41284430). -

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

- -

Cardiovascular phenotype

Benign:1

Mar 09, 2015

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

0.062

Mutation Taster

=91/9

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.48

dbscSNV1_RF

Benign

0.51

SpliceAI score (max)

0.48

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.48

Position offset: 5

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