rs12665088

Positions:

• chr6-123418586-G-A
• chr6-123418586-G-C
• chr6-123418586-G-T

Variant summary

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

The NM_006073.4(TRDN):​c.1051+19477C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 151,736 control chromosomes in the GnomAD database, including 11,338 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 0.38 (11338 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRDN NM_006073.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.396

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRDN	NM_006073.4	c.1051+19477C>T		intron_variant		ENST00000334268.9	NP_006064.2
TRDN	NM_001251987.2	c.1054+19477C>T		intron_variant			NP_001238916.1
TRDN	NM_001407315.1	c.994+19477C>T		intron_variant			NP_001394244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRDN	ENST00000334268.9	c.1051+19477C>T		intron_variant		1	NM_006073.4	ENSP00000333984.5
TRDN	ENST00000662930.1	c.1054+19477C>T		intron_variant				ENSP00000499585.1
TRDN-AS1	ENST00000587106.6	n.304+1G>A		splice_donor_variant, intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57134 AN: 151618 Hom.: 11330 Cov.: 31

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.375

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.377 AC: 57194 AN: 151736 Hom.: 11338 Cov.: 31 AF XY: 0.389 AC XY: 28800 AN XY: 74120

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.708

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.375

Alfa AF: 0.373 Hom.: 14217

Bravo AF: 0.368

Asia WGS AF: 0.553 AC: 1917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.4
DANN	Benign	0.23

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: rs12665088; hg19: chr6-123739731;