ENST00000628709.2:c.887_889delTTT

Variant names:

• chr6-123464887-GAAA-G
• rs201431159
• ENST00000628709.2:c.887_889delTTT

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The ENST00000628709.2(TRDN):​c.887_889delTTT​(p.Phe296del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000766 in 1,306,092 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: TRDN ENST00000628709.2 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in ENST00000628709.2. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRDN	NM_006073.4	c.931+16_931+18delTTT		intron_variant	Intron 10 of 40	ENST00000334268.9	NP_006064.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRDN	ENST00000334268.9	c.931+16_931+18delTTT		intron_variant	Intron 10 of 40	1	NM_006073.4	ENSP00000333984.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.66e-7 AC: 1 AN: 1306092 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 643432

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29646

American (AMR) AF: 0.00 AC: 0 AN: 32568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22802

East Asian (EAS) AF: 0.00 AC: 0 AN: 33472

South Asian (SAS) AF: 0.00 AC: 0 AN: 71588

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45812

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5330

European-Non Finnish (NFE) AF: 9.89e-7 AC: 1 AN: 1011286

Other (OTH) AF: 0.00 AC: 0 AN: 53588

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8

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: rs201431159; hg19: chr6-123786032;