6-123392972-C-T

Variant names:

• chr6-123392972-C-T
• rs11154152
• NM_006073.4:c.1105+652G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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-AS1 (HGNC:40592): (TRDN antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

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.1105+652G>A		intron	N/A	NP_006064.2
	TRDN	NM_001251987.2		c.1108+652G>A		intron	N/A	NP_001238916.1
	TRDN	NM_001407315.1		c.1048+652G>A		intron	N/A	NP_001394244.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRDN	ENST00000334268.9	TSL:1 MANE Select	c.1105+652G>A		intron	N/A	ENSP00000333984.5
	TRDN	ENST00000962661.1		c.1108+652G>A		intron	N/A	ENSP00000632720.1
	TRDN	ENST00000962654.1		c.1108+652G>A		intron	N/A	ENSP00000632713.1

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

African (AFR) AF: 0.687 AC: 28482 AN: 41440

American (AMR) AF: 0.554 AC: 8428 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1913 AN: 3470

East Asian (EAS) AF: 0.258 AC: 1331 AN: 5160

South Asian (SAS) AF: 0.256 AC: 1234 AN: 4818

European-Finnish (FIN) AF: 0.407 AC: 4293 AN: 10550

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33748 AN: 67834

Other (OTH) AF: 0.577 AC: 1208 AN: 2094

Alfa AF: 0.519 Hom.: 7228

Bravo AF: 0.559

Asia WGS AF: 0.373 AC: 1301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.017
DANN	Benign	0.27
PhyloP100		-3.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs11154152; hg19: chr6-123714117;