rs1358855

Variant names:

• chr6-123573591-C-A
• rs1358855
• NM_006073.4:c.23-2459G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006073.4(TRDN):​c.23-2459G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 151,694 control chromosomes in the GnomAD database, including 22,941 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (22941 hom., cov: 32)
• Consequence: TRDN NM_006073.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRDN	NM_006073.4	c.23-2459G>T		intron_variant	Intron 1 of 40	ENST00000334268.9	NP_006064.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRDN	ENST00000334268.9	c.23-2459G>T		intron_variant	Intron 1 of 40	1	NM_006073.4	ENSP00000333984.5

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83142 AN: 151574 Hom.: 22913 Cov.: 32

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.536

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.549 AC: 83224 AN: 151694 Hom.: 22941 Cov.: 32 AF XY: 0.549 AC XY: 40720 AN XY: 74128

African (AFR) AF: 0.528 AC: 21877 AN: 41406

American (AMR) AF: 0.571 AC: 8703 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1905 AN: 3460

East Asian (EAS) AF: 0.525 AC: 2693 AN: 5134

South Asian (SAS) AF: 0.504 AC: 2431 AN: 4820

European-Finnish (FIN) AF: 0.564 AC: 5940 AN: 10534

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 37998 AN: 67798

Other (OTH) AF: 0.534 AC: 1125 AN: 2106

Alfa AF: 0.552 Hom.: 3900

Bravo AF: 0.550

Asia WGS AF: 0.483 AC: 1678 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.7
DANN	Benign	0.20
PhyloP100		0.040
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: rs1358855; hg19: chr6-123894736;