GeneBe

NM_006073.4:c.1083G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_006073.4(TRDN):​c.1083G>A​(p.Gly361Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,454,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G361G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TRDN
NM_006073.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.425

Publications

0 publications found
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 was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP7
Synonymous conserved (PhyloP=-0.425 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRDNNM_006073.4 linkc.1083G>A p.Gly361Gly synonymous_variant Exon 13 of 41 ENST00000334268.9 NP_006064.2 Q13061-1
TRDNNM_001251987.2 linkc.1086G>A p.Gly362Gly synonymous_variant Exon 13 of 21 NP_001238916.1 A0A590UJV0Q8IVK2
TRDNNM_001407315.1 linkc.1026G>A p.Gly342Gly synonymous_variant Exon 12 of 20 NP_001394244.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRDNENST00000334268.9 linkc.1083G>A p.Gly361Gly synonymous_variant Exon 13 of 41 1 NM_006073.4 ENSP00000333984.5 Q13061-1
TRDNENST00000662930.1 linkc.1086G>A p.Gly362Gly synonymous_variant Exon 13 of 21 ENSP00000499585.1 A0A590UJV0
TRDN-AS1ENST00000587106.6 linkn.55+4171C>T intron_variant Intron 1 of 8 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000837
AC:
2
AN:
238934
AF XY:
0.00000772
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000186
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1454674
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
723070
show subpopulations
⚠️ 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:
33346
American (AMR)
AF:
0.00
AC:
0
AN:
44036
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25872
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39608
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85164
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52930
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5744
European-Non Finnish (NFE)
AF:
0.00000181
AC:
2
AN:
1107980
Other (OTH)
AF:
0.00
AC:
0
AN:
59994
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000081), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.300
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
CADD
Benign
2.7
DANN
Benign
0.68
PhyloP100
-0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs878854815; hg19: chr6-123714791; API