19-55156942-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000363.5(TNNI3):c.108+108G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,279,782 control chromosomes in the GnomAD database, including 54,530 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 13201 hom., cov: 32)

Exomes 𝑓: 0.25 ( 41329 hom. )

Consequence

TNNI3
NM_000363.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -7.55

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

hypertrophic cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
dilated cardiomyopathy 2A
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
hypertrophic cardiomyopathy 7
Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
cardiomyopathy, familial restrictive, 1
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
dilated cardiomyopathy 1FF
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
dilated cardiomyopathy
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial isolated restrictive cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
arrhythmogenic right ventricular cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

TNNI3 links:

ENSG00000267110 (HGNC:):

ENSG00000267110 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 19-55156942-C-G is Benign according to our data. Variant chr19-55156942-C-G is described in ClinVar as [Benign]. Clinvar id is 1245765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
TNNI3	NM_000363.5 link	c.108+108G>C		intron_variant	Intron 3 of 7	ENST00000344887.10	NP_000354.4	P19429Q6FGX2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNNI3	ENST00000344887.10 link	c.108+108G>C		intron_variant	Intron 3 of 7	1	NM_000363.5	ENSP00000341838.5		P19429
ENSG00000267110	ENST00000587871.1 link	n.*210+108G>C		intron_variant	Intron 6 of 8	5		ENSP00000473050.1		M0R381

Frequencies

GnomAD3 genomes

AF:

0.366

AC:

55528

AN:

151868

Hom.:

13161

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:

0.361

GnomAD4 exome

AF:

0.248

AC:

279347

AN:

1127796

Hom.:

41329

Cov.:

AF XY:

0.251

AC XY:

142031

AN XY:

566316

show subpopulations

African (AFR)

AF:

0.673

AC:

17824

AN:

26474

American (AMR)

AF:

0.481

AC:

16980

AN:

35286

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

5062

AN:

23496

East Asian (EAS)

AF:

0.421

AC:

14521

AN:

34512

South Asian (SAS)

AF:

0.412

AC:

30361

AN:

73780

European-Finnish (FIN)

AF:

0.231

AC:

8149

AN:

35216

Middle Eastern (MID)

AF:

0.327

AC:

1175

AN:

3596

European-Non Finnish (NFE)

AF:

0.202

AC:

171246

AN:

846214

Other (OTH)

AF:

0.285

AC:

14029

AN:

49222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

10943

21886

32830

43773

54716

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.366

AC:

55636

AN:

151986

Hom.:

13201

Cov.:

AF XY:

0.368

AC XY:

27314

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.658

AC:

27239

AN:

41414

American (AMR)

AF:

0.405

AC:

6183

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.214

AC:

744

AN:

3470

East Asian (EAS)

AF:

0.441

AC:

2269

AN:

5144

South Asian (SAS)

AF:

0.441

AC:

2126

AN:

4826

European-Finnish (FIN)

AF:

0.226

AC:

2394

AN:

10576

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.201

AC:

13683

AN:

67966

Other (OTH)

AF:

0.367

AC:

774

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

1556

3112

4668

6224

7780

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.116

Hom.:

169

Bravo

AF:

0.392

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.015

(source)

DANN

Benign

0.33

PhyloP100

-7.6

PromoterAI

0.16

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

19-55156942-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over