Variant 19-55157437-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000363.5(TNNI3):c.12-129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,580,076 control chromosomes in the GnomAD database, including 64,130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.37 ( 13194 hom., cov: 32)

Exomes 𝑓: 0.24 ( 50936 hom. )

Consequence

TNNI3
NM_000363.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.130

Variant links:

Genes affected

TNNI3 (HGNC:11947): (troponin I3, cardiac type) Troponin I (TnI), along with troponin T (TnT) and troponin C (TnC), is one of 3 subunits that form the troponin complex of the thin filaments of striated muscle. TnI is the inhibitory subunit; blocking actin-myosin interactions and thereby mediating striated muscle relaxation. The TnI subfamily contains three genes: TnI-skeletal-fast-twitch, TnI-skeletal-slow-twitch, and TnI-cardiac. This gene encodes the TnI-cardiac protein and is exclusively expressed in cardiac muscle tissues. Mutations in this gene cause familial hypertrophic cardiomyopathy type 7 (CMH7) and familial restrictive cardiomyopathy (RCM). Troponin I is useful in making a diagnosis of heart failure, and of ischemic heart disease. An elevated level of troponin is also now used as indicator of acute myocardial injury in patients hospitalized with moderate/severe Coronavirus Disease 2019 (COVID-19). Such elevation has also been associated with higher risk of mortality in cardiovascular disease patients hospitalized due to COVID-19. [provided by RefSeq, Aug 2020]

TNNI3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 19-55157437-T-C is Benign according to our data. Variant chr19-55157437-T-C is described in ClinVar as [Benign]. Clinvar id is 1264197.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNNI3	NM_000363.5 linkuse as main transcript	c.12-129A>G		intron_variant		ENST00000344887.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNNI3	ENST00000344887.10 linkuse as main transcript	c.12-129A>G		intron_variant		1	NM_000363.5	P1

Frequencies

GnomAD3 genomes

AF:

0.365

AC:

55478

AN:

151830

Hom.:

13154

Cov.:

show subpopulations

Gnomad AFR

AF:

0.657

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.404

Gnomad ASJ

AF:

0.214

Gnomad EAS

AF:

0.441

Gnomad SAS

AF:

0.441

Gnomad FIN

AF:

0.226

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.360

GnomAD4 exome

AF:

0.245

AC:

349428

AN:

1428128

Hom.:

50936

Cov.:

AF XY:

0.248

AC XY:

175709

AN XY:

709880

show subpopulations

Gnomad4 AFR exome

AF:

0.677

Gnomad4 AMR exome

AF:

0.490

Gnomad4 ASJ exome

AF:

0.213

Gnomad4 EAS exome

AF:

0.421

Gnomad4 SAS exome

AF:

0.414

Gnomad4 FIN exome

AF:

0.231

Gnomad4 NFE exome

AF:

0.201

Gnomad4 OTH exome

AF:

0.282

GnomAD4 genome

AF:

0.366

AC:

55586

AN:

151948

Hom.:

13194

Cov.:

AF XY:

0.367

AC XY:

27288

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.658

Gnomad4 AMR

AF:

0.404

Gnomad4 ASJ

AF:

0.214

Gnomad4 EAS

AF:

0.441

Gnomad4 SAS

AF:

0.440

Gnomad4 FIN

AF:

0.226

Gnomad4 NFE

AF:

0.201

Gnomad4 OTH

AF:

0.367

Alfa

AF:

0.291

Hom.:

3028

Bravo

AF:

0.392

Asia WGS

AF:

0.521

AC:

1809

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.8

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over