rs150412658

Variant names:

• chr6-123497220-T-C
• rs150412658
• NM_006073.4:c.826A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006073.4(TRDN):​c.826A>G​(p.Ile276Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000962 in 1,559,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000078 (0 hom.)
• Consequence: TRDN NM_006073.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 3.62
• Publications: 2 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-AS1 (HGNC:40592): (TRDN antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09707701).

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.826A>G	p.Ile276Val	missense	Exon 9 of 41	NP_006064.2	Q13061-1
	TRDN	NM_001251987.2		c.826A>G	p.Ile276Val	missense	Exon 9 of 21	NP_001238916.1	A0A590UJV0
	TRDN	NM_001407315.1		c.793+6499A>G		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.826A>G	p.Ile276Val	missense	Exon 9 of 41	ENSP00000333984.5	Q13061-1
	TRDN	ENST00000628709.2	TSL:1	c.793+6499A>G		intron	N/A	ENSP00000486095.1	Q13061-2
	TRDN	ENST00000962661.1		c.826A>G	p.Ile276Val	missense	Exon 9 of 41	ENSP00000632720.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152102 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000562 AC: 1 AN: 178018 AF XY: 0.0000105

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000406

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000782 AC: 11 AN: 1407406 Hom.: 0 Cov.: 29 AF XY: 0.00000574 AC XY: 4 AN XY: 696430

African (AFR) AF: 0.00 AC: 0 AN: 31088

American (AMR) AF: 0.0000564 AC: 2 AN: 35478

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24864

East Asian (EAS) AF: 0.00 AC: 0 AN: 36890

South Asian (SAS) AF: 0.00 AC: 0 AN: 78344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51130

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5646

European-Non Finnish (NFE) AF: 0.00000553 AC: 6 AN: 1085794

Other (OTH) AF: 0.0000344 AC: 2 AN: 58172

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152220 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74430

African (AFR) AF: 0.0000241 AC: 1 AN: 41574

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67962

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Cardiovascular phenotype (1)
-	1	-	Catecholaminergic polymorphic ventricular tachycardia 1 (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Benign	0.64
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		3.6
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.073
Sift	Uncertain	0.015	D
Sift4G	Benign	0.41	T
Polyphen		0.0040	B
Vest4		0.24
MVP		0.45
ClinPred		0.082	T
GERP RS		6.0
Varity_R		0.086
gMVP		0.011
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs150412658; hg19: chr6-123818365;