rs367962513

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1

The NM_006073.4(TRDN):c.1472-13C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000907 in 1,609,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

TRDN
NM_006073.4 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.67

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]

TRDN links:

LOC124901393 (HGNC:):

LOC124901393 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 6-123316508-G-A is Benign according to our data. Variant chr6-123316508-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 504835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0000659 (96/1457386) while in subpopulation AFR AF= 0.00183 (61/33276). AF 95% confidence interval is 0.00146. There are 0 homozygotes in gnomad4_exome. There are 33 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRDN	NM_006073.4 linkuse as main transcript	c.1472-13C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000334268.9
LOC124901393	XR_007059734.1 linkuse as main transcript	n.81+7071G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRDN	ENST00000334268.9 linkuse as main transcript	c.1472-13C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_006073.4	A2	Q13061-1

Frequencies

GnomAD3 genomes

AF:

0.000310

AC:

AN:

151566

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000992

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000264

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000122

AC:

AN:

246864

Hom.:

AF XY:

0.000119

AC XY:

AN XY:

133966

show subpopulations

Gnomad AFR exome

AF:

0.00130

Gnomad AMR exome

AF:

0.0000878

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000112

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000895

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000659

AC:

AN:

1457386

Hom.:

Cov.:

AF XY:

0.0000455

AC XY:

AN XY:

725082

show subpopulations

Gnomad4 AFR exome

AF:

0.00183

Gnomad4 AMR exome

AF:

0.0000900

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000761

Gnomad4 SAS exome

AF:

0.0000581

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.000150

GnomAD4 genome

AF:

0.000330

AC:

AN:

151684

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

AN XY:

74102

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.000264

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000485

Hom.:

Bravo

AF:

0.000461

Asia WGS

AF:

0.000578

AC:

AN:

3472

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jun 13, 2016

c.1472-13C>T in intron 23 of TRDN: This variant is not expected to have clinical significance because a C>T change at this position does not diverge from the sp lice consensus sequence and is therefore unlikely to impact splicing. It has bee n identified in 0.1% (13/9714) of African chromosomes by the Exome Aggregation C onsortium (ExAC, http://exac.broadinstitute.org; dbSNP rs367962513). -

Catecholaminergic polymorphic ventricular tachycardia 1;C3809536:Catecholaminergic polymorphic ventricular tachycardia 5

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 01, 2021

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 18, 2020

- -

Catecholaminergic polymorphic ventricular tachycardia 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 11, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

Cadd

Benign

8.4

Dann

Benign

0.46

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

Publications

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over