chr6-123218464-C-T

Position:

• chr6-123218464-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.*137G>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 0.444 in 995,068 control chromosomes in the GnomAD database, including 100,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (14151 hom., cov: 32)
  • Exomes 𝑓: 0.45 (85866 hom.)
• Consequence: TRDN NM_006073.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.49

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=-0.92).
• BP6: Variant 6-123218464-C-T is Benign according to our data. Variant chr6-123218464-C-T is described in ClinVar as [Benign]. Clinvar id is 1226229.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRDN	NM_006073.4	c.*137G>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	c.*137G>A		3_prime_UTR_variant	41/41	1	NM_006073.4	ENSP00000333984.5

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64483 AN: 151602 Hom.: 14130 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.486

GnomAD4 exome AF: 0.447 AC: 376845 AN: 843348 Hom.: 85866 Cov.: 11 AF XY: 0.441 AC XY: 186053 AN XY: 422128

Gnomad4 AFR exome AF: 0.352

Gnomad4 AMR exome AF: 0.587

Gnomad4 ASJ exome AF: 0.502

Gnomad4 EAS exome AF: 0.312

Gnomad4 SAS exome AF: 0.292

Gnomad4 FIN exome AF: 0.362

Gnomad4 NFE exome AF: 0.468

Gnomad4 OTH exome AF: 0.446

GnomAD4 genome AF: 0.425 AC: 64554 AN: 151720 Hom.: 14151 Cov.: 32 AF XY: 0.420 AC XY: 31159 AN XY: 74134

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.467

Gnomad4 OTH AF: 0.491

Alfa AF: 0.465 Hom.: 6706

Bravo AF: 0.444

Asia WGS AF: 0.352 AC: 1221 AN: 3476

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	-0.92
CADD	Benign	4.2
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: rs361509; hg19: chr6-123539609; COSMIC: COSV62136218;