rs1358856

Positions:

• chr6-123573833-C-A
• chr6-123573833-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000334268.9(TRDN):​c.23-2701G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,760 control chromosomes in the GnomAD database, including 22,891 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 (22891 hom., cov: 32)
• Consequence: TRDN ENST00000334268.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.487

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=-0.92).
• 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	Protein	UniProt
TRDN	NM_006073.4	c.23-2701G>T		intron_variant		ENST00000334268.9	NP_006064.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRDN	ENST00000334268.9	c.23-2701G>T		intron_variant		1	NM_006073.4	ENSP00000333984	A2

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83079 AN: 151642 Hom.: 22863 Cov.: 32

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.548 AC: 83161 AN: 151760 Hom.: 22891 Cov.: 32 AF XY: 0.548 AC XY: 40650 AN XY: 74148

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.571

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.535

Alfa AF: 0.486 Hom.: 2481

Bravo AF: 0.550

Asia WGS AF: 0.486 AC: 1680 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.16
DANN	Benign	0.31

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: rs1358856; hg19: chr6-123894978;