rs11154152

chr6-123392972-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006073.4(TRDN):c.1105+652G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 151,796 control chromosomes in the GnomAD database, including 22,681 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (22681 hom., cov: 32)
• Consequence: TRDN NM_006073.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.65

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRDN	NM_006073.4	c.1105+652G>A		intron_variant		ENST00000334268.9
TRDN	NM_001251987.2	c.1108+652G>A		intron_variant
TRDN	NM_001407315.1	c.1048+652G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRDN	ENST00000334268.9	c.1105+652G>A		intron_variant		1	NM_006073.4	A2
TRDN-AS1	ENST00000587106.6	n.55+3497C>T		intron_variant, non_coding_transcript_variant		5
TRDN	ENST00000662930.1	c.1108+652G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81119 AN: 151678 Hom.: 22627 Cov.: 32

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.574

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.535 AC: 81241 AN: 151796 Hom.: 22681 Cov.: 32 AF XY: 0.525 AC XY: 38929 AN XY: 74192

Gnomad4 AFR AF: 0.687

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.577

Alfa AF: 0.515 Hom.: 4176

Bravo AF: 0.559

Asia WGS AF: 0.373 AC: 1301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.017
Dann	Benign	0.27

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

Other links and lift over

dbSNP: rs11154152; hg19: chr6-123714117;