chr6-123393512-C-T

Position:

• chr6-123393512-C-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+112G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 885,388 control chromosomes in the GnomAD database, including 6,895 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1743 hom., cov: 32)
  • Exomes 𝑓: 0.11 (5152 hom.)
• Consequence: TRDN NM_006073.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.134

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=-0.86).
• BP6: Variant 6-123393512-C-T is Benign according to our data. Variant chr6-123393512-C-T is described in ClinVar as [Benign]. Clinvar id is 1296363.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRDN	NM_006073.4	c.1105+112G>A		intron_variant		ENST00000334268.9	NP_006064.2
TRDN	NM_001251987.2	c.1108+112G>A		intron_variant			NP_001238916.1
TRDN	NM_001407315.1	c.1048+112G>A		intron_variant			NP_001394244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRDN	ENST00000334268.9	c.1105+112G>A		intron_variant		1	NM_006073.4	ENSP00000333984	A2
TRDN-AS1	ENST00000587106.6	n.55+4037C>T		intron_variant, non_coding_transcript_variant		5
TRDN	ENST00000662930.1	c.1108+112G>A		intron_variant				ENSP00000499585

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22675 AN: 151356 Hom.: 1730 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0647

Gnomad SAS AF: 0.0691

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.160

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.113 AC: 82823 AN: 733914 Hom.: 5152 AF XY: 0.111 AC XY: 41750 AN XY: 374568

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.114

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.0469

Gnomad4 SAS exome AF: 0.0594

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.123

GnomAD4 genome AF: 0.150 AC: 22728 AN: 151474 Hom.: 1743 Cov.: 32 AF XY: 0.150 AC XY: 11126 AN XY: 73980

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.0640

Gnomad4 SAS AF: 0.0691

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.151

Alfa AF: 0.140 Hom.: 181

Bravo AF: 0.153

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 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.46

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: rs73771941; hg19: chr6-123714657; COSMIC: COSV62125529;