rs3813328

Variant names:

• chr6-123381354-G-A
• rs3813328
• NM_006073.4:c.1186+16C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-123381354-G-A
• chr6-123381354-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006073.4(TRDN):​c.1186+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,543,182 control chromosomes in the GnomAD database, including 110,777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (10184 hom., cov: 31)
  • Exomes 𝑓: 0.36 (100593 hom.)
• Consequence: TRDN NM_006073.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.794
• Publications: 5 publications found

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]

TRDN Gene-Disease associations (from GenCC):

• catecholaminergic polymorphic ventricular tachycardia

  Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• catecholaminergic polymorphic ventricular tachycardia 5

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• familial long QT syndrome

  Inheritance: AR Classification: STRONG Submitted by: G2P
• long QT syndrome

  Inheritance: AR Classification: STRONG Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 6-123381354-G-A is Benign according to our data. Variant chr6-123381354-G-A is described in ClinVar as Benign. ClinVar VariationId is 259914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006073.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRDN	NM_006073.4	MANE Select	c.1186+16C>T		intron	N/A	NP_006064.2	Q13061-1
	TRDN	NM_001251987.2		c.1189+16C>T		intron	N/A	NP_001238916.1	A0A590UJV0
	TRDN	NM_001407315.1		c.1129+16C>T		intron	N/A	NP_001394244.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRDN	ENST00000334268.9	TSL:1 MANE Select	c.1186+16C>T		intron	N/A	ENSP00000333984.5	Q13061-1
	TRDN	ENST00000962661.1		c.1189+16C>T		intron	N/A	ENSP00000632720.1
	TRDN	ENST00000962654.1		c.1186+16C>T		intron	N/A	ENSP00000632713.1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53083 AN: 151612 Hom.: 10189 Cov.: 31

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.309

GnomAD2 exomes AF: 0.413 AC: 68761 AN: 166302 AF XY: 0.428

Gnomad AFR exome AF: 0.256

Gnomad AMR exome AF: 0.373

Gnomad ASJ exome AF: 0.275

Gnomad EAS exome AF: 0.727

Gnomad FIN exome AF: 0.469

Gnomad NFE exome AF: 0.322

Gnomad OTH exome AF: 0.352

GnomAD4 exome AF: 0.364 AC: 507007 AN: 1391452 Hom.: 100593 Cov.: 31 AF XY: 0.374 AC XY: 257033 AN XY: 687252

African (AFR) AF: 0.254 AC: 8067 AN: 31820

American (AMR) AF: 0.373 AC: 13532 AN: 36298

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 6801 AN: 25058

East Asian (EAS) AF: 0.734 AC: 26723 AN: 36432

South Asian (SAS) AF: 0.653 AC: 51616 AN: 78994

European-Finnish (FIN) AF: 0.469 AC: 22712 AN: 48434

Middle Eastern (MID) AF: 0.330 AC: 1860 AN: 5640

European-Non Finnish (NFE) AF: 0.331 AC: 354972 AN: 1071026

Other (OTH) AF: 0.359 AC: 20724 AN: 57750

GnomAD4 genome AF: 0.350 AC: 53094 AN: 151730 Hom.: 10184 Cov.: 31 AF XY: 0.364 AC XY: 27006 AN XY: 74156

African (AFR) AF: 0.264 AC: 10915 AN: 41412

American (AMR) AF: 0.332 AC: 5055 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 931 AN: 3466

East Asian (EAS) AF: 0.740 AC: 3822 AN: 5164

South Asian (SAS) AF: 0.672 AC: 3235 AN: 4816

European-Finnish (FIN) AF: 0.486 AC: 5121 AN: 10530

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.338 AC: 22952 AN: 67822

Other (OTH) AF: 0.308 AC: 650 AN: 2112

Alfa AF: 0.328 Hom.: 3863

Bravo AF: 0.329

Asia WGS AF: 0.590 AC: 2048 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	1	Catecholaminergic polymorphic ventricular tachycardia 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.3
DANN	Benign	0.73
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3813328; hg19: chr6-123702499;