chr6-123394268-C-A

Position:

• chr6-123394268-C-A

Variant summary

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

The NM_006073.4(TRDN):​c.1052-591G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 151,338 control chromosomes in the GnomAD database, including 2,108 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 0.16 (2108 hom., cov: 32)
• Consequence: TRDN NM_006073.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRDN	NM_006073.4	c.1052-591G>T		intron_variant		ENST00000334268.9
TRDN	NM_001251987.2	c.1055-591G>T		intron_variant
TRDN	NM_001407315.1	c.995-591G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRDN	ENST00000334268.9	c.1052-591G>T		intron_variant		1	NM_006073.4	A2
TRDN-AS1	ENST00000587106.6	n.55+4793C>A		intron_variant, non_coding_transcript_variant		5
TRDN	ENST00000662930.1	c.1055-591G>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24519 AN: 151226 Hom.: 2108 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0805

Gnomad EAS AF: 0.0927

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.162 AC: 24516 AN: 151338 Hom.: 2108 Cov.: 32 AF XY: 0.163 AC XY: 12050 AN XY: 73918

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.0805

Gnomad4 EAS AF: 0.0922

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.133

Alfa AF: 0.168 Hom.: 277

Bravo AF: 0.152

Asia WGS AF: 0.164 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.62
DANN	Benign	0.32

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: rs12661427; hg19: chr6-123715413; COSMIC: COSV62116571;