rs3729843

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001276345.2(TNNT2):c.164-50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 1,606,412 control chromosomes in the GnomAD database, including 151,414 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 11003 hom., cov: 32)

Exomes 𝑓: 0.43 ( 140411 hom. )

Consequence

TNNT2
NM_001276345.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.359

Publications

18 publications found

Variant links:

Genes affected

TNNT2 (HGNC:11949): (troponin T2, cardiac type) This gene encodes the cardiac isoform of troponin T. The encoded protein is the tropomyosin-binding subunit of the troponin complex, which is located on the thin filament of striated muscles and regulates muscle contraction in response to alterations in intracellular calcium ion concentration. Mutations in this gene have been associated with familial hypertrophic cardiomyopathy as well as with dilated cardiomyopathy. [provided by RefSeq, May 2022]

TNNT2 Gene-Disease associations (from GenCC):

dilated cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
dilated cardiomyopathy 1D
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
hypertrophic cardiomyopathy 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
hypertrophic cardiomyopathy 3
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
cardiomyopathy, familial restrictive, 3
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
hypertrophic 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
left ventricular noncompaction
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
cardiomyopathy
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
arrhythmogenic right ventricular cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

TNNT2 links:

ENSG00000286600 (HGNC:):

ENSG00000286600 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=-0.83).

BP6

Variant 1-201367856-C-T is Benign according to our data. Variant chr1-201367856-C-T is described in ClinVar as Benign. ClinVar VariationId is 256843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001276345.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNNT2	NM_001276345.2	MANE Select	c.164-50G>A	intron	N/A	NP_001263274.1	P45379-1
TNNT2	NM_000364.4		c.164-50G>A	intron	N/A	NP_000355.2
TNNT2	NM_001406723.1		c.164-50G>A	intron	N/A	NP_001393652.1	P45379-10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNNT2	ENST00000656932.1	MANE Select	c.164-50G>A	intron	N/A	ENSP00000499593.1	P45379-1
TNNT2	ENST00000367322.6	TSL:1	c.134-53G>A	intron	N/A	ENSP00000356291.2	A0A499FJM7
TNNT2	ENST00000367320.6	TSL:1	c.164-53G>A	intron	N/A	ENSP00000356289.2	P45379-12

Frequencies

GnomAD3 genomes

AF:

0.341

AC:

51760

AN:

151840

Hom.:

10991

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0817

Gnomad AMI

AF:

0.306

Gnomad AMR

AF:

0.452

Gnomad ASJ

AF:

0.402

Gnomad EAS

AF:

0.201

Gnomad SAS

AF:

0.421

Gnomad FIN

AF:

0.490

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.453

Gnomad OTH

AF:

0.342

GnomAD2 exomes

AF:

0.418

AC:

105001

AN:

251296

AF XY:

0.425

show subpopulations

Gnomad AFR exome

AF:

0.0714

Gnomad AMR exome

AF:

0.519

Gnomad ASJ exome

AF:

0.404

Gnomad EAS exome

AF:

0.203

Gnomad FIN exome

AF:

0.476

Gnomad NFE exome

AF:

0.454

Gnomad OTH exome

AF:

0.438

GnomAD4 exome

AF:

0.433

AC:

629887

AN:

1454454

Hom.:

140411

Cov.:

AF XY:

0.435

AC XY:

314744

AN XY:

724020

show subpopulations

African (AFR)

AF:

0.0657

AC:

2184

AN:

33254

American (AMR)

AF:

0.512

AC:

22881

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.413

AC:

10771

AN:

26104

East Asian (EAS)

AF:

0.204

AC:

8101

AN:

39642

South Asian (SAS)

AF:

0.434

AC:

37355

AN:

86116

European-Finnish (FIN)

AF:

0.479

AC:

25488

AN:

53256

Middle Eastern (MID)

AF:

0.380

AC:

2184

AN:

5746

European-Non Finnish (NFE)

AF:

0.449

AC:

496199

AN:

1105480

Other (OTH)

AF:

0.411

AC:

24724

AN:

60136

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

19680

39360

59039

78719

98399

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14678

29356

44034

58712

73390

<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:

0.341

AC:

51782

AN:

151958

Hom.:

11003

Cov.:

AF XY:

0.345

AC XY:

25612

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.0814

AC:

3379

AN:

41496

American (AMR)

AF:

0.454

AC:

6919

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.402

AC:

1395

AN:

3466

East Asian (EAS)

AF:

0.202

AC:

1041

AN:

5160

South Asian (SAS)

AF:

0.421

AC:

2023

AN:

4804

European-Finnish (FIN)

AF:

0.490

AC:

5174

AN:

10552

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.453

AC:

30754

AN:

67904

Other (OTH)

AF:

0.342

AC:

723

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1517

3033

4550

6066

7583

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<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:

0.383

Hom.:

21760

Bravo

AF:

0.327

Asia WGS

AF:

0.325

AC:

1131

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Cardiomyopathy, familial restrictive, 3 (1)

Dilated cardiomyopathy 1D (1)

Hypertrophic cardiomyopathy 2 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.4

(source)

DANN

Benign

0.84

PhyloP100

0.36

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over