6-123599427-T-C

Variant names:

• chr6-123599427-T-C
• rs941815
• NM_006073.4:c.23-28295A>G

Variant summary

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

The NM_006073.4(TRDN):​c.23-28295A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 151,902 control chromosomes in the GnomAD database, including 23,474 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 (23474 hom., cov: 32)
• Consequence: TRDN NM_006073.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.984
• Publications: 5 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

ENSG00000285941 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRDN	NM_006073.4	c.23-28295A>G		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.23-28295A>G		intron_variant	Intron 1 of 40	1	NM_006073.4	ENSP00000333984.5

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83594 AN: 151784 Hom.: 23454 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.574

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

GnomAD4 genome AF: 0.551 AC: 83659 AN: 151902 Hom.: 23474 Cov.: 32 AF XY: 0.551 AC XY: 40882 AN XY: 74192

African (AFR) AF: 0.447 AC: 18518 AN: 41444

American (AMR) AF: 0.655 AC: 9969 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2071 AN: 3468

East Asian (EAS) AF: 0.449 AC: 2308 AN: 5146

South Asian (SAS) AF: 0.500 AC: 2402 AN: 4806

European-Finnish (FIN) AF: 0.587 AC: 6201 AN: 10568

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.591 AC: 40178 AN: 67928

Other (OTH) AF: 0.573 AC: 1207 AN: 2106

Alfa AF: 0.566 Hom.: 4848

Bravo AF: 0.555

Asia WGS AF: 0.472 AC: 1639 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.60
PhyloP100		0.98
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: rs941815; hg19: chr6-123920572;