chr6-123218539-C-T

Variant names:

• chr6-123218539-C-T
• rs361508
• NM_006073.4:c.*62G>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.*62G>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 0.797 in 1,548,600 control chromosomes in the GnomAD database, including 496,581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.83 (52671 hom., cov: 32)
  • Exomes 𝑓: 0.79 (443910 hom.)
• Consequence: TRDN NM_006073.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.443
• Publications: 12 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=-0.88).
• BP6: Variant 6-123218539-C-T is Benign according to our data. Variant chr6-123218539-C-T is described in ClinVar as Benign. ClinVar VariationId is 1296366.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006073.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRDN	NM_006073.4	MANE Select	c.*62G>A		3_prime_UTR	Exon 41 of 41	NP_006064.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRDN	ENST00000334268.9	TSL:1 MANE Select	c.*62G>A		3_prime_UTR	Exon 41 of 41	ENSP00000333984.5

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125318 AN: 151568 Hom.: 52614 Cov.: 32

Gnomad AFR AF: 0.953

Gnomad AMI AF: 0.821

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.853

GnomAD4 exome AF: 0.794 AC: 1108568 AN: 1396916 Hom.: 443910 Cov.: 22 AF XY: 0.789 AC XY: 545403 AN XY: 691098

African (AFR) AF: 0.961 AC: 29917 AN: 31124

American (AMR) AF: 0.844 AC: 30434 AN: 36058

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 18015 AN: 22396

East Asian (EAS) AF: 0.499 AC: 19370 AN: 38850

South Asian (SAS) AF: 0.665 AC: 51320 AN: 77180

European-Finnish (FIN) AF: 0.676 AC: 34620 AN: 51206

Middle Eastern (MID) AF: 0.774 AC: 4217 AN: 5446

European-Non Finnish (NFE) AF: 0.812 AC: 875097 AN: 1077200

Other (OTH) AF: 0.793 AC: 45578 AN: 57456

GnomAD4 genome AF: 0.827 AC: 125438 AN: 151684 Hom.: 52671 Cov.: 32 AF XY: 0.817 AC XY: 60523 AN XY: 74106

African (AFR) AF: 0.953 AC: 39507 AN: 41458

American (AMR) AF: 0.853 AC: 12966 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 2782 AN: 3468

East Asian (EAS) AF: 0.509 AC: 2604 AN: 5116

South Asian (SAS) AF: 0.645 AC: 3108 AN: 4820

European-Finnish (FIN) AF: 0.666 AC: 7018 AN: 10534

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.807 AC: 54678 AN: 67786

Other (OTH) AF: 0.855 AC: 1797 AN: 2102

Alfa AF: 0.827 Hom.: 65465

Bravo AF: 0.850

Asia WGS AF: 0.653 AC: 2273 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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.49
DANN	Benign	0.36
PhyloP100		-0.44
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: rs361508; hg19: chr6-123539684; COSMIC: COSV107392647;