6-123218540-T-C

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.*61A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 1,549,128 control chromosomes in the GnomAD database, including 171,394 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (18252 hom., cov: 32)
  • Exomes 𝑓: 0.47 (153142 hom.)
• Consequence: TRDN NM_006073.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.626

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=-0.85).
• BP6: Variant 6-123218540-T-C is Benign according to our data. Variant chr6-123218540-T-C is described in ClinVar as [Benign]. Clinvar id is 1263065.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRDN	NM_006073.4	c.*61A>G		3_prime_UTR_variant	41/41	ENST00000334268.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRDN	ENST00000334268.9	c.*61A>G		3_prime_UTR_variant	41/41	1	NM_006073.4	A2

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73817 AN: 151496 Hom.: 18223 Cov.: 32

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.529

GnomAD4 exome AF: 0.465 AC: 650073 AN: 1397516 Hom.: 153142 Cov.: 23 AF XY: 0.460 AC XY: 318359 AN XY: 691428

Gnomad4 AFR exome AF: 0.564

Gnomad4 AMR exome AF: 0.629

Gnomad4 ASJ exome AF: 0.503

Gnomad4 EAS exome AF: 0.358

Gnomad4 SAS exome AF: 0.365

Gnomad4 FIN exome AF: 0.372

Gnomad4 NFE exome AF: 0.471

Gnomad4 OTH exome AF: 0.466

GnomAD4 genome AF: 0.487 AC: 73908 AN: 151612 Hom.: 18252 Cov.: 32 AF XY: 0.483 AC XY: 35801 AN XY: 74074

Gnomad4 AFR AF: 0.547

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.535

Alfa AF: 0.437 Hom.: 3404

Bravo AF: 0.511

Asia WGS AF: 0.427 AC: 1484 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.6
Dann	Benign	0.72

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: rs1259; hg19: chr6-123539685; COSMIC: COSV62122848;