NM_006073.4:c.480T>G

Variant names:

• chr6-123530510-A-C
• rs1020844292
• NM_006073.4:c.480T>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 2P and 9B. PM2 BP6_Very_Strong BP7

The NM_006073.4(TRDN):​c.480T>G​(p.Thr160Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000032 in 1,248,636 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T160T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: TRDN NM_006073.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0500
• 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: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• catecholaminergic polymorphic ventricular tachycardia 5

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

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

  Inheritance: AR Classification: STRONG Submitted by: ClinGen

ENSG00000285691 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 6-123530510-A-C is Benign according to our data. Variant chr6-123530510-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1111646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.05 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRDN	NM_006073.4	MANE Select	c.480T>G	p.Thr160Thr	synonymous	Exon 5 of 41	NP_006064.2
	TRDN	NM_001251987.2		c.480T>G	p.Thr160Thr	synonymous	Exon 5 of 21	NP_001238916.1
	TRDN	NM_001407315.1		c.480T>G	p.Thr160Thr	synonymous	Exon 5 of 20	NP_001394244.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRDN	ENST00000334268.9	TSL:1 MANE Select	c.480T>G	p.Thr160Thr	synonymous	Exon 5 of 41	ENSP00000333984.5
	TRDN	ENST00000628709.2	TSL:1	c.480T>G	p.Thr160Thr	synonymous	Exon 5 of 9	ENSP00000486095.1
	TRDN	ENST00000546248.6	TSL:1	c.480T>G	p.Thr160Thr	synonymous	Exon 5 of 8	ENSP00000439281.2

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151820 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1096816 Hom.: 0 Cov.: 19 AF XY: 0.00000185 AC XY: 1 AN XY: 540346

African (AFR) AF: 0.00 AC: 0 AN: 22498

American (AMR) AF: 0.00 AC: 0 AN: 17624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19802

East Asian (EAS) AF: 0.00 AC: 0 AN: 26916

South Asian (SAS) AF: 0.00 AC: 0 AN: 56806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4116

European-Non Finnish (NFE) AF: 0.00000231 AC: 2 AN: 864654

Other (OTH) AF: 0.00 AC: 0 AN: 45070

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151820 Hom.: 0 Cov.: 33 AF XY: 0.0000270 AC XY: 2 AN XY: 74128

African (AFR) AF: 0.00 AC: 0 AN: 41404

American (AMR) AF: 0.00 AC: 0 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 298

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67864

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.000112 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Cardiovascular phenotype (1)
-	-	1	Catecholaminergic polymorphic ventricular tachycardia 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.7
DANN	Benign	0.69
PhyloP100		-0.050
PromoterAI		0.011	Neutral

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

Other links and lift over

dbSNP: rs1020844292; hg19: chr6-123851655;