rs41284430

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006073.4(TRDN):​c.1105+5G>C variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

TRDN
NM_006073.4 splice_donor_5th_base, intron

Scores

2
Splicing: ADA: 0.2093
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0620
Variant links:
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)

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRDNNM_006073.4 linkuse as main transcriptc.1105+5G>C splice_donor_5th_base_variant, intron_variant ENST00000334268.9
TRDNNM_001251987.2 linkuse as main transcriptc.1108+5G>C splice_donor_5th_base_variant, intron_variant
TRDNNM_001407315.1 linkuse as main transcriptc.1048+5G>C splice_donor_5th_base_variant, intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRDNENST00000334268.9 linkuse as main transcriptc.1105+5G>C splice_donor_5th_base_variant, intron_variant 1 NM_006073.4 A2Q13061-1
TRDN-AS1ENST00000587106.6 linkuse as main transcriptn.55+4144C>G intron_variant, non_coding_transcript_variant 5
TRDNENST00000662930.1 linkuse as main transcriptc.1108+5G>C splice_donor_5th_base_variant, intron_variant

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
CADD
Benign
11
DANN
Benign
0.81

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.21
dbscSNV1_RF
Benign
0.49
SpliceAI score (max)
0.54
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.54
Position offset: 5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-123714764; API