6-123352527-AT-ATT

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PVS1_ModerateBP6BS1

The NM_001251987.2(TRDN):c.1383dupA(p.Ter462MetfsTer28) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000528 in 1,592,678 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. K461K) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00043 ( 0 hom. )

Consequence

TRDN
NM_001251987.2 frameshift

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 1.05

Publications

0 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: Likely_benign. The variant received -3 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.00216 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

BP6

Variant 6-123352527-A-AT is Benign according to our data. Variant chr6-123352527-A-AT is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 229346.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0015 (226/150548) while in subpopulation AFR AF = 0.00471 (194/41146). AF 95% confidence interval is 0.00417. There are 0 homozygotes in GnomAd4. There are 109 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001251987.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TRDN	NM_006073.4	MANE Select	c.1369+11dupA		intron	N/A	NP_006064.2
TRDN	NM_001251987.2		c.1383dupA	p.Ter462MetfsTer28	frameshift	Exon 21 of 21	NP_001238916.1
TRDN	NM_001407315.1		c.1323dupA	p.Ter442MetfsTer28	frameshift	Exon 20 of 20	NP_001394244.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TRDN	ENST00000334268.9	TSL:1 MANE Select	c.1369+11dupA		intron	N/A	ENSP00000333984.5
TRDN	ENST00000662930.1		c.1383dupA	p.Ter462MetfsTer28	frameshift	Exon 21 of 21	ENSP00000499585.1
TRDN	ENST00000962661.1		c.1372+11dupA		intron	N/A	ENSP00000632720.1

Frequencies

GnomAD3 genomes

AF:

0.00150

AC:

226

AN:

150436

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00473

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000268

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000962

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000311

Gnomad OTH

AF:

0.00244

GnomAD2 exomes

AF:

0.000774

AC:

162

AN:

209292

AF XY:

0.000704

show subpopulations

Gnomad AFR exome

AF:

0.00653

Gnomad AMR exome

AF:

0.000596

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000677

Gnomad FIN exome

AF:

0.000103

Gnomad NFE exome

AF:

0.000401

Gnomad OTH exome

AF:

0.00124

GnomAD4 exome

AF:

0.000426

AC:

615

AN:

1442130

Hom.:

Cov.:

AF XY:

0.000406

AC XY:

291

AN XY:

717114

show subpopulations

African (AFR)

AF:

0.00560

AC:

184

AN:

32844

American (AMR)

AF:

0.000466

AC:

AN:

42896

Ashkenazi Jewish (ASJ)

AF:

0.0000787

AC:

AN:

25400

East Asian (EAS)

AF:

0.000129

AC:

AN:

38844

South Asian (SAS)

AF:

0.000251

AC:

AN:

83718

European-Finnish (FIN)

AF:

0.0000191

AC:

AN:

52386

Middle Eastern (MID)

AF:

0.000352

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.000314

AC:

346

AN:

1100978

Other (OTH)

AF:

0.000572

AC:

AN:

59390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

107

134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.00150

AC:

226

AN:

150548

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

109

AN XY:

73494

show subpopulations

African (AFR)

AF:

0.00471

AC:

194

AN:

41146

American (AMR)

AF:

0.000267

AC:

AN:

14960

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3436

East Asian (EAS)

AF:

0.000194

AC:

AN:

5142

South Asian (SAS)

AF:

0.00

AC:

AN:

4764

European-Finnish (FIN)

AF:

0.0000962

AC:

AN:

10400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000311

AC:

AN:

67428

Other (OTH)

AF:

0.00242

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00115

Hom.:

Bravo

AF:

0.00160

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

Catecholaminergic polymorphic ventricular tachycardia 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.1

Mutation Taster

=99/1

polymorphism

(source)

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over