chr6-123393511-G-T

Position:

• chr6-123393511-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006073.4(TRDN):​c.1105+113C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 855,280 control chromosomes in the GnomAD database, including 5,800 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1652 hom., cov: 32)
  • Exomes 𝑓: 0.11 (4148 hom.)
• Consequence: TRDN NM_006073.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.99

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-123393511-G-T is Benign according to our data. Variant chr6-123393511-G-T is described in ClinVar as [Benign]. Clinvar id is 1256874.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRDN	NM_006073.4	c.1105+113C>A		intron_variant		ENST00000334268.9	NP_006064.2
TRDN	NM_001251987.2	c.1108+113C>A		intron_variant			NP_001238916.1
TRDN	NM_001407315.1	c.1048+113C>A		intron_variant			NP_001394244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRDN	ENST00000334268.9	c.1105+113C>A		intron_variant		1	NM_006073.4	ENSP00000333984.5
TRDN	ENST00000662930.1	c.1108+113C>A		intron_variant				ENSP00000499585.1
TRDN-AS1	ENST00000587106.6	n.55+4036G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22287 AN: 150458 Hom.: 1642 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0509

Gnomad SAS AF: 0.0688

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.160

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.110 AC: 77734 AN: 704706 Hom.: 4148 AF XY: 0.109 AC XY: 39271 AN XY: 360756

Gnomad4 AFR exome AF: 0.192

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.0401

Gnomad4 SAS exome AF: 0.0580

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.112

Gnomad4 OTH exome AF: 0.118

GnomAD4 genome AF: 0.148 AC: 22337 AN: 150574 Hom.: 1652 Cov.: 32 AF XY: 0.149 AC XY: 10934 AN XY: 73510

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.0506

Gnomad4 SAS AF: 0.0689

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.148

Alfa AF: 0.0437 Hom.: 31

Bravo AF: 0.150

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.16
DANN	Benign	0.54

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: rs73771940; hg19: chr6-123714656;