6-123337680-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006073.4(TRDN):​c.1370-11C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,409,608 control chromosomes in the GnomAD database, including 30,454 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3551 hom., cov: 32)
Exomes 𝑓: 0.18 ( 26903 hom. )

Consequence

TRDN
NM_006073.4 intron

Scores

2
Splicing: ADA: 0.002238
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.950
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 6-123337680-G-T is Benign according to our data. Variant chr6-123337680-G-T is described in ClinVar as [Benign]. Clinvar id is 227111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-123337680-G-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRDNNM_006073.4 linkc.1370-11C>A intron_variant Intron 21 of 40 ENST00000334268.9 NP_006064.2 Q13061-1
LOC105377984XR_942947.3 linkn.262G>T non_coding_transcript_exon_variant Exon 3 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRDNENST00000334268.9 linkc.1370-11C>A intron_variant Intron 21 of 40 1 NM_006073.4 ENSP00000333984.5 Q13061-1

Frequencies

GnomAD3 genomes
AF:
0.185
AC:
28076
AN:
151812
Hom.:
3550
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0845
Gnomad AMI
AF:
0.130
Gnomad AMR
AF:
0.215
Gnomad ASJ
AF:
0.194
Gnomad EAS
AF:
0.630
Gnomad SAS
AF:
0.412
Gnomad FIN
AF:
0.275
Gnomad MID
AF:
0.228
Gnomad NFE
AF:
0.176
Gnomad OTH
AF:
0.171
GnomAD3 exomes
AF:
0.249
AC:
32103
AN:
129056
Hom.:
5123
AF XY:
0.256
AC XY:
17534
AN XY:
68620
show subpopulations
Gnomad AFR exome
AF:
0.0807
Gnomad AMR exome
AF:
0.278
Gnomad ASJ exome
AF:
0.200
Gnomad EAS exome
AF:
0.607
Gnomad SAS exome
AF:
0.381
Gnomad FIN exome
AF:
0.270
Gnomad NFE exome
AF:
0.168
Gnomad OTH exome
AF:
0.215
GnomAD4 exome
AF:
0.177
AC:
222199
AN:
1257678
Hom.:
26903
Cov.:
21
AF XY:
0.183
AC XY:
114115
AN XY:
622224
show subpopulations
Gnomad4 AFR exome
AF:
0.0678
Gnomad4 AMR exome
AF:
0.263
Gnomad4 ASJ exome
AF:
0.184
Gnomad4 EAS exome
AF:
0.657
Gnomad4 SAS exome
AF:
0.366
Gnomad4 FIN exome
AF:
0.245
Gnomad4 NFE exome
AF:
0.145
Gnomad4 OTH exome
AF:
0.179
GnomAD4 genome
AF:
0.185
AC:
28091
AN:
151930
Hom.:
3551
Cov.:
32
AF XY:
0.198
AC XY:
14671
AN XY:
74246
show subpopulations
Gnomad4 AFR
AF:
0.0847
Gnomad4 AMR
AF:
0.215
Gnomad4 ASJ
AF:
0.194
Gnomad4 EAS
AF:
0.630
Gnomad4 SAS
AF:
0.413
Gnomad4 FIN
AF:
0.275
Gnomad4 NFE
AF:
0.176
Gnomad4 OTH
AF:
0.168
Alfa
AF:
0.136
Hom.:
375
Bravo
AF:
0.174
Asia WGS
AF:
0.411
AC:
1420
AN:
3464

ClinVar

Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:5
Nov 24, 2014
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

1370-11C>A in intron 21 of TRDN: This variant is not expected to have clinical s ignificance because it has been identified in 15.0% (794/5284) of European Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs9401658). -

Apr 09, 2023
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Oct 14, 2016
Eurofins Ntd Llc (ga)
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Sep 22, 2016
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1
Feb 04, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Catecholaminergic polymorphic ventricular tachycardia 5 Benign:1
Sep 10, 2021
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
10
DANN
Benign
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0022
dbscSNV1_RF
Benign
0.21
SpliceAI score (max)
0.13
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs9401658; hg19: chr6-123658825; API