Variant 6-123352527-AT-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PVS1_ModeratePM2BS1

The NM_001251987.2(TRDN):c.1383delA(p.Lys461fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,436,530 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: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRDN
NM_001251987.2 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.00216 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00019 (273/1436530) while in subpopulation AMR AF= 0.0013 (55/42402). AF 95% confidence interval is 0.00102. There are 0 homozygotes in gnomad4_exome. There are 140 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRDN	NM_006073.4 link	c.1369+11delA		intron_variant		ENST00000334268.9	NP_006064.2	Q13061-1
TRDN	NM_001251987.2 link	c.1383delA	p.Lys461fs	frameshift_variant	21/21		NP_001238916.1	A0A590UJV0Q8IVK2
TRDN	NM_001407315.1 link	c.1323delA	p.Lys441fs	frameshift_variant	20/20		NP_001394244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRDN	ENST00000334268.9 link	c.1369+11delA		intron_variant		1	NM_006073.4	ENSP00000333984.5		Q13061-1
TRDN	ENST00000662930.1 link	c.1383delA	p.Lys461fs	frameshift_variant	21/21			ENSP00000499585.1		A0A590UJV0

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150430

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000190

AC:

273

AN:

1436530

Hom.:

Cov.:

AF XY:

0.000196

AC XY:

140

AN XY:

714160

show subpopulations

Gnomad4 AFR exome

AF:

0.000459

Gnomad4 AMR exome

AF:

0.00130

Gnomad4 ASJ exome

AF:

0.000555

Gnomad4 EAS exome

AF:

0.000129

Gnomad4 SAS exome

AF:

0.000446

Gnomad4 FIN exome

AF:

0.000192

Gnomad4 NFE exome

AF:

0.000109

Gnomad4 OTH exome

AF:

0.000271

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

150430

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73370

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00629

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over