6-123393512-C-T

Variant names:

• chr6-123393512-C-T
• rs73771941
• NM_006073.4:c.1105+112G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRDN	NM_006073.4	MANE Select	c.1105+112G>A		intron	N/A	NP_006064.2	Q13061-1
	TRDN	NM_001251987.2		c.1108+112G>A		intron	N/A	NP_001238916.1	A0A590UJV0
	TRDN	NM_001407315.1		c.1048+112G>A		intron	N/A	NP_001394244.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRDN	ENST00000334268.9	TSL:1 MANE Select	c.1105+112G>A		intron	N/A	ENSP00000333984.5	Q13061-1
	TRDN	ENST00000962661.1		c.1108+112G>A		intron	N/A	ENSP00000632720.1
	TRDN	ENST00000962654.1		c.1108+112G>A		intron	N/A	ENSP00000632713.1

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

African (AFR) AF: 0.199 AC: 3088 AN: 15510

American (AMR) AF: 0.114 AC: 1801 AN: 15786

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 2434 AN: 15810

East Asian (EAS) AF: 0.0469 AC: 1403 AN: 29898

South Asian (SAS) AF: 0.0594 AC: 2763 AN: 46544

European-Finnish (FIN) AF: 0.141 AC: 6109 AN: 43392

Middle Eastern (MID) AF: 0.145 AC: 526 AN: 3638

European-Non Finnish (NFE) AF: 0.114 AC: 60536 AN: 529452

Other (OTH) AF: 0.123 AC: 4163 AN: 33884

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

African (AFR) AF: 0.209 AC: 8650 AN: 41328

American (AMR) AF: 0.132 AC: 2001 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 555 AN: 3460

East Asian (EAS) AF: 0.0640 AC: 330 AN: 5154

South Asian (SAS) AF: 0.0691 AC: 333 AN: 4816

European-Finnish (FIN) AF: 0.151 AC: 1584 AN: 10488

Middle Eastern (MID) AF: 0.172 AC: 50 AN: 290

European-Non Finnish (NFE) AF: 0.129 AC: 8727 AN: 67740

Other (OTH) AF: 0.151 AC: 317 AN: 2096

Alfa AF: 0.140 Hom.: 181

Bravo AF: 0.153

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.46
PhyloP100		-0.13
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: rs73771941; hg19: chr6-123714657; COSMIC: COSV62125529;