6-123218540-T-C

Variant names:

• chr6-123218540-T-C
• rs1259
• NM_006073.4:c.*61A>G

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.*61A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 1,549,128 control chromosomes in the GnomAD database, including 171,394 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (18252 hom., cov: 32)
  • Exomes 𝑓: 0.47 (153142 hom.)
• Consequence: TRDN NM_006073.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.626
• Publications: 10 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=-0.85).
• BP6: Variant 6-123218540-T-C is Benign according to our data. Variant chr6-123218540-T-C is described in ClinVar as [Benign]. Clinvar id is 1263065.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRDN	NM_006073.4	c.*61A>G		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.*61A>G		3_prime_UTR_variant	Exon 41 of 41	1	NM_006073.4	ENSP00000333984.5

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73817 AN: 151496 Hom.: 18223 Cov.: 32

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.529

GnomAD4 exome AF: 0.465 AC: 650073 AN: 1397516 Hom.: 153142 Cov.: 23 AF XY: 0.460 AC XY: 318359 AN XY: 691428

African (AFR) AF: 0.564 AC: 17515 AN: 31050

American (AMR) AF: 0.629 AC: 22581 AN: 35916

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 11272 AN: 22400

East Asian (EAS) AF: 0.358 AC: 13926 AN: 38858

South Asian (SAS) AF: 0.365 AC: 28215 AN: 77364

European-Finnish (FIN) AF: 0.372 AC: 19065 AN: 51242

Middle Eastern (MID) AF: 0.527 AC: 2874 AN: 5454

European-Non Finnish (NFE) AF: 0.471 AC: 507809 AN: 1077748

Other (OTH) AF: 0.466 AC: 26816 AN: 57484

GnomAD4 genome AF: 0.487 AC: 73908 AN: 151612 Hom.: 18252 Cov.: 32 AF XY: 0.483 AC XY: 35801 AN XY: 74074

African (AFR) AF: 0.547 AC: 22631 AN: 41404

American (AMR) AF: 0.570 AC: 8663 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1757 AN: 3468

East Asian (EAS) AF: 0.359 AC: 1838 AN: 5116

South Asian (SAS) AF: 0.366 AC: 1760 AN: 4814

European-Finnish (FIN) AF: 0.364 AC: 3845 AN: 10558

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31742 AN: 67764

Other (OTH) AF: 0.535 AC: 1122 AN: 2098

Alfa AF: 0.451 Hom.: 6196

Bravo AF: 0.511

Asia WGS AF: 0.427 AC: 1484 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.72
PhyloP100		0.63
Mutation Taster		=100/0	polymorphism (auto)

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: rs1259; hg19: chr6-123539685; COSMIC: COSV62122848;