rs7754205

Positions:

• chr6-123218759-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000334268.9(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 ENST00000334268.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.929

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]

ACMG classification

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/exons	MANE	Protein	UniProt
TRDN	NM_006073.4	c.2051-19G>A		intron_variant		ENST00000334268.9	NP_006064.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRDN	ENST00000334268.9	c.2051-19G>A		intron_variant		1	NM_006073.4	ENSP00000333984	A2

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64429 AN: 151440 Hom.: 14120 Cov.: 31

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

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.: 34 AF XY: 0.447 AC XY: 308699 AN XY: 690788

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.: 31 AF XY: 0.420 AC XY: 31110 AN XY: 74044

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

Submissions by phenotype

not specified Benign:5

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jul 08, 2021	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 21, 2016	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. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Catecholaminergic polymorphic ventricular tachycardia 5 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

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

Other links and lift over

dbSNP: rs7754205; hg19: chr6-123539904;