rs77049316

Variant names:

• chr6-123218381-G-A
• rs77049316
• NM_006073.4:c.*220C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006073.4(TRDN):​c.*220C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0074 in 446,566 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (74 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (25 hom.)
• Consequence: TRDN NM_006073.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.398
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 6-123218381-G-A is Benign according to our data. Variant chr6-123218381-G-A is described in ClinVar as [Benign]. Clinvar id is 1283183.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRDN	NM_006073.4	c.*220C>T		3_prime_UTR_variant	Exon 41 of 41	ENST00000334268.9	NP_006064.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRDN	ENST00000334268.9	c.*220C>T		3_prime_UTR_variant	Exon 41 of 41	1	NM_006073.4	ENSP00000333984.5

Frequencies

GnomAD3 genomes AF: 0.0174 AC: 2638 AN: 151678 Hom.: 73 Cov.: 32

Gnomad AFR AF: 0.0599

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00769

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.00225 AC: 663 AN: 294770 Hom.: 25 Cov.: 4 AF XY: 0.00203 AC XY: 311 AN XY: 152854

African (AFR) AF: 0.0595 AC: 513 AN: 8626

American (AMR) AF: 0.00519 AC: 55 AN: 10596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9738

East Asian (EAS) AF: 0.0000447 AC: 1 AN: 22382

South Asian (SAS) AF: 0.000104 AC: 2 AN: 19286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20524

Middle Eastern (MID) AF: 0.000713 AC: 1 AN: 1402

European-Non Finnish (NFE) AF: 0.0000923 AC: 17 AN: 184164

Other (OTH) AF: 0.00410 AC: 74 AN: 18052

GnomAD4 genome AF: 0.0174 AC: 2643 AN: 151796 Hom.: 74 Cov.: 32 AF XY: 0.0166 AC XY: 1230 AN XY: 74180

African (AFR) AF: 0.0598 AC: 2479 AN: 41422

American (AMR) AF: 0.00768 AC: 117 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5120

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 67842

Other (OTH) AF: 0.0138 AC: 29 AN: 2108

Alfa AF: 0.0105 Hom.: 10

Bravo AF: 0.0195

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 21, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.0
DANN	Benign	0.28
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs77049316; hg19: chr6-123539526;