rs1358855

Positions:

• chr6-123573591-C-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TRDN	NM_006073.4	c.23-2459G>T		intron_variant		ENST00000334268.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRDN	ENST00000334268.9	c.23-2459G>T		intron_variant		1	NM_006073.4	A2

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

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.571

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.534

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1358855; hg19: chr6-123894736;