6-123218464-C-T

Variant names:

• chr6-123218464-C-T
• rs361509
• NM_006073.4:c.*137G>A

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.*137G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 995,068 control chromosomes in the GnomAD database, including 100,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (14151 hom., cov: 32)
  • Exomes 𝑓: 0.45 (85866 hom.)
• Consequence: TRDN NM_006073.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.49
• Publications: 8 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=-0.92).
• BP6: Variant 6-123218464-C-T is Benign according to our data. Variant chr6-123218464-C-T is described in ClinVar as [Benign]. Clinvar id is 1226229.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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 rank	MANE	Protein	UniProt
TRDN	NM_006073.4	c.*137G>A		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.*137G>A		3_prime_UTR_variant	Exon 41 of 41	1	NM_006073.4	ENSP00000333984.5

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64483 AN: 151602 Hom.: 14130 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.486

GnomAD4 exome AF: 0.447 AC: 376845 AN: 843348 Hom.: 85866 Cov.: 11 AF XY: 0.441 AC XY: 186053 AN XY: 422128

African (AFR) AF: 0.352 AC: 6865 AN: 19482

American (AMR) AF: 0.587 AC: 11004 AN: 18744

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 7881 AN: 15698

East Asian (EAS) AF: 0.312 AC: 10187 AN: 32652

South Asian (SAS) AF: 0.292 AC: 15265 AN: 52214

European-Finnish (FIN) AF: 0.362 AC: 12375 AN: 34178

Middle Eastern (MID) AF: 0.504 AC: 1744 AN: 3458

European-Non Finnish (NFE) AF: 0.468 AC: 294392 AN: 628530

Other (OTH) AF: 0.446 AC: 17132 AN: 38392

GnomAD4 genome AF: 0.425 AC: 64554 AN: 151720 Hom.: 14151 Cov.: 32 AF XY: 0.420 AC XY: 31159 AN XY: 74134

African (AFR) AF: 0.348 AC: 14429 AN: 41408

American (AMR) AF: 0.552 AC: 8402 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1744 AN: 3464

East Asian (EAS) AF: 0.317 AC: 1626 AN: 5122

South Asian (SAS) AF: 0.288 AC: 1387 AN: 4818

European-Finnish (FIN) AF: 0.353 AC: 3723 AN: 10546

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.467 AC: 31659 AN: 67838

Other (OTH) AF: 0.491 AC: 1033 AN: 2102

Alfa AF: 0.464 Hom.: 8028

Bravo AF: 0.444

Asia WGS AF: 0.352 AC: 1221 AN: 3476

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	-0.92
CADD	Benign	4.2
DANN	Benign	0.36
PhyloP100		1.5
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: rs361509; hg19: chr6-123539609; COSMIC: COSV62136218;