chr19-55156191-G-C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_000363.5(TNNI3):​c.282+10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,612,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

TNNI3
NM_000363.5 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.921

Publications

0 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant 19-55156191-G-C is Benign according to our data. Variant chr19-55156191-G-C is described in CliVar as Likely_benign. Clinvar id is 525067.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-55156191-G-C is described in CliVar as Likely_benign. Clinvar id is 525067.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-55156191-G-C is described in CliVar as Likely_benign. Clinvar id is 525067.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-55156191-G-C is described in CliVar as Likely_benign. Clinvar id is 525067.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-55156191-G-C is described in CliVar as Likely_benign. Clinvar id is 525067.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-55156191-G-C is described in CliVar as Likely_benign. Clinvar id is 525067.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-55156191-G-C is described in CliVar as Likely_benign. Clinvar id is 525067.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-55156191-G-C is described in CliVar as Likely_benign. Clinvar id is 525067.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-55156191-G-C is described in CliVar as Likely_benign. Clinvar id is 525067.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-55156191-G-C is described in CliVar as Likely_benign. Clinvar id is 525067.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-55156191-G-C is described in CliVar as Likely_benign. Clinvar id is 525067.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-55156191-G-C is described in CliVar as Likely_benign. Clinvar id is 525067.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TNNI3NM_000363.5 linkc.282+10C>G intron_variant Intron 5 of 7 ENST00000344887.10 NP_000354.4 P19429Q6FGX2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TNNI3ENST00000344887.10 linkc.282+10C>G intron_variant Intron 5 of 7 1 NM_000363.5 ENSP00000341838.5 P19429
ENSG00000267110ENST00000587871.1 linkn.*384+10C>G intron_variant Intron 8 of 8 5 ENSP00000473050.1 M0R381

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152096
Hom.:
0
Cov.:
32
show subpopulations
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00000413
AC:
1
AN:
242278
AF XY:
0.00000752
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:
0.00000926
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000753
AC:
11
AN:
1460534
Hom.:
0
Cov.:
32
AF XY:
0.00000826
AC XY:
6
AN XY:
726610
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33474
American (AMR)
AF:
0.00
AC:
0
AN:
44704
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26124
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39694
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52312
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00000989
AC:
11
AN:
1111840
Other (OTH)
AF:
0.00
AC:
0
AN:
60362
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.480
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152096
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74284
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41388
American (AMR)
AF:
0.00
AC:
0
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5184
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4838
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10608
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000441
AC:
3
AN:
68010
Other (OTH)
AF:
0.00
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000189

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

TNNI3-related disorder Benign:1
Oct 02, 2020
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Hypertrophic cardiomyopathy Benign:1
Jan 06, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely 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
-0.55
CADD
Benign
13
DANN
Benign
0.91
PhyloP100
0.92
Mutation Taster
=100/0
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.15
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: rs974607293; hg19: chr19-55667559; API