rs55704802

Variant names:

• chr6-123278360-A-C
• rs55704802
• NM_006073.4:c.1538-13T>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_006073.4(TRDN):​c.1538-13T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00746 in 1,272,424 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0063 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0076 (43 hom.)
• Consequence: TRDN NM_006073.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.745
• Publications: 0 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 -16 ACMG points.

• BP6: Variant 6-123278360-A-C is Benign according to our data. Variant chr6-123278360-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 227113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00634 (965/152232) while in subpopulation NFE AF = 0.00995 (677/68012). AF 95% confidence interval is 0.00933. There are 6 homozygotes in GnomAd4. There are 453 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR,AD gene

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.1538-13T>G		intron	N/A	NP_006064.2	Q13061-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRDN	ENST00000334268.9	TSL:1 MANE Select	c.1538-13T>G		intron	N/A	ENSP00000333984.5	Q13061-1
	TRDN	ENST00000962661.1		c.1541-13T>G		intron	N/A	ENSP00000632720.1
	TRDN	ENST00000962654.1		c.1538-13T>G		intron	N/A	ENSP00000632713.1

Frequencies

GnomAD3 genomes AF: 0.00634 AC: 965 AN: 152114 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00754

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00123

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00995

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00648 AC: 749 AN: 115502 AF XY: 0.00602

Gnomad AFR exome AF: 0.000893

Gnomad AMR exome AF: 0.00382

Gnomad ASJ exome AF: 0.0188

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00123

Gnomad NFE exome AF: 0.0108

Gnomad OTH exome AF: 0.00644

GnomAD4 exome AF: 0.00761 AC: 8526 AN: 1120192 Hom.: 43 Cov.: 18 AF XY: 0.00750 AC XY: 4148 AN XY: 552836

African (AFR) AF: 0.000995 AC: 24 AN: 24116

American (AMR) AF: 0.00430 AC: 92 AN: 21376

Ashkenazi Jewish (ASJ) AF: 0.0171 AC: 357 AN: 20830

East Asian (EAS) AF: 0.00 AC: 0 AN: 28700

South Asian (SAS) AF: 0.000401 AC: 26 AN: 64870

European-Finnish (FIN) AF: 0.00120 AC: 46 AN: 38480

Middle Eastern (MID) AF: 0.00556 AC: 27 AN: 4860

European-Non Finnish (NFE) AF: 0.00877 AC: 7638 AN: 870712

Other (OTH) AF: 0.00683 AC: 316 AN: 46248

GnomAD4 genome AF: 0.00634 AC: 965 AN: 152232 Hom.: 6 Cov.: 33 AF XY: 0.00608 AC XY: 453 AN XY: 74450

African (AFR) AF: 0.00180 AC: 75 AN: 41552

American (AMR) AF: 0.00753 AC: 115 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00123 AC: 13 AN: 10596

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00995 AC: 677 AN: 68012

Other (OTH) AF: 0.0104 AC: 22 AN: 2116

Alfa AF: 0.00881 Hom.: 4

Bravo AF: 0.00664

Asia WGS AF: 0.000870 AC: 3 AN: 3462

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	3	not specified (3)
-	-	1	Catecholaminergic polymorphic ventricular tachycardia 1 (1)
-	-	1	Catecholaminergic polymorphic ventricular tachycardia 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.6
DANN	Benign	0.73
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: -1
DS_AL_spliceai		0.32		Position offset: -13

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

Other links and lift over

dbSNP: rs55704802; hg19: chr6-123599505;