rs361508

Positions:

• chr6-123218539-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRDN	NM_006073.4	c.*62G>A		3_prime_UTR_variant	41/41	ENST00000334268.9	NP_006064.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRDN	ENST00000334268.9	c.*62G>A		3_prime_UTR_variant	41/41	1	NM_006073.4	ENSP00000333984	A2

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

Gnomad4 AFR exome AF: 0.961

Gnomad4 AMR exome AF: 0.844

Gnomad4 ASJ exome AF: 0.804

Gnomad4 EAS exome AF: 0.499

Gnomad4 SAS exome AF: 0.665

Gnomad4 FIN exome AF: 0.676

Gnomad4 NFE exome AF: 0.812

Gnomad4 OTH exome AF: 0.793

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

Gnomad4 AFR AF: 0.953

Gnomad4 AMR AF: 0.853

Gnomad4 ASJ AF: 0.802

Gnomad4 EAS AF: 0.509

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.807

Gnomad4 OTH AF: 0.855

Alfa AF: 0.821 Hom.: 49341

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.49
DANN	Benign	0.36

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: rs361508; hg19: chr6-123539684;