11-1922820-CCTCTCTCTCT-CCTCTCTCTCTCT

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001367847.1(TNNT3):c.-36_-35dupCT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,450,634 control chromosomes in the GnomAD database, including 991 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.063 ( 934 hom., cov: 31)

Exomes 𝑓: 0.0082 ( 57 hom. )

Consequence

TNNT3
NM_001367847.1 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.77

Publications

0 publications found

Variant links:

Genes affected

TNNT3 (HGNC:11950): (troponin T3, fast skeletal type) The binding of Ca(2+) to the trimeric troponin complex initiates the process of muscle contraction. Increased Ca(2+) concentrations produce a conformational change in the troponin complex that is transmitted to tropomyosin dimers situated along actin filaments. The altered conformation permits increased interaction between a myosin head and an actin filament which, ultimately, produces a muscle contraction. The troponin complex has protein subunits C, I, and T. Subunit C binds Ca(2+) and subunit I binds to actin and inhibits actin-myosin interaction. Subunit T binds the troponin complex to the tropomyosin complex and is also required for Ca(2+)-mediated activation of actomyosin ATPase activity. There are 3 different troponin T genes that encode tissue-specific isoforms of subunit T for fast skeletal-, slow skeletal-, and cardiac-muscle. This gene encodes fast skeletal troponin T protein; also known as troponin T type 3. Alternative splicing results in multiple transcript variants encoding additional distinct troponin T type 3 isoforms. A developmentally regulated switch between fetal/neonatal and adult troponin T type 3 isoforms occurs. Additional splice variants have been described but their biological validity has not been established. Mutations in this gene may cause distal arthrogryposis multiplex congenita type 2B (DA2B). [provided by RefSeq, Oct 2009]

TNNT3 Gene-Disease associations (from GenCC):

arthrogryposis, distal, type 2B2
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia
distal arthrogryposis type 2B1
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
congenital myopathy
Inheritance: AR Classification: STRONG Submitted by: G2P
nemaline myopathy
Inheritance: AR Classification: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics
digitotalar dysmorphism
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Sheldon-hall syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TNNT3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 11-1922820-C-CCT is Benign according to our data. Variant chr11-1922820-C-CCT is described in ClinVar as Benign. ClinVar VariationId is 1250023.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367847.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNNT3	NM_006757.4	MANE Select	c.-18-18_-18-17dupCT	intron	N/A	NP_006748.1	P45378-2
TNNT3	NM_001367847.1		c.-36_-35dupCT	5_prime_UTR	Exon 1 of 16	NP_001354776.1	P45378-3
TNNT3	NM_001367842.1		c.-36_-35dupCT	5_prime_UTR	Exon 1 of 15	NP_001354771.1	P45378-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNNT3	ENST00000278317.11	TSL:5 MANE Select	c.-18-18_-18-17dupCT	intron	N/A	ENSP00000278317.6	P45378-2
TNNT3	ENST00000381589.7	TSL:1	c.-18-18_-18-17dupCT	intron	N/A	ENSP00000371001.3	P45378-6
TNNT3	ENST00000381579.7	TSL:1	c.-18-18_-18-17dupCT	intron	N/A	ENSP00000370991.3	P45378-4

Frequencies

GnomAD3 genomes

AF:

0.0626

AC:

9348

AN:

149402

Hom.:

933

Cov.:

show subpopulations

Gnomad AFR

AF:

0.213

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0273

Gnomad ASJ

AF:

0.0172

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00126

Gnomad FIN

AF:

0.000101

Gnomad MID

AF:

0.00962

Gnomad NFE

AF:

0.00116

Gnomad OTH

AF:

0.0530

GnomAD4 exome

AF:

0.00817

AC:

10631

AN:

1301130

Hom.:

Cov.:

AF XY:

0.00722

AC XY:

4707

AN XY:

651926

show subpopulations

African (AFR)

AF:

0.207

AC:

6359

AN:

30760

American (AMR)

AF:

0.0188

AC:

797

AN:

42454

Ashkenazi Jewish (ASJ)

AF:

0.0173

AC:

420

AN:

24296

East Asian (EAS)

AF:

0.000299

AC:

AN:

36822

South Asian (SAS)

AF:

0.00158

AC:

130

AN:

82254

European-Finnish (FIN)

AF:

0.000824

AC:

AN:

46096

Middle Eastern (MID)

AF:

0.0147

AC:

AN:

5392

European-Non Finnish (NFE)

AF:

0.00190

AC:

1857

AN:

978454

Other (OTH)

AF:

0.0172

AC:

940

AN:

54602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.418

Heterozygous variant carriers

442

883

1325

1766

2208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

252

504

756

1008

1260

<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:

0.0627

AC:

9367

AN:

149504

Hom.:

934

Cov.:

AF XY:

0.0605

AC XY:

4415

AN XY:

72966

show subpopulations

African (AFR)

AF:

0.213

AC:

8702

AN:

40846

American (AMR)

AF:

0.0273

AC:

410

AN:

15030

Ashkenazi Jewish (ASJ)

AF:

0.0172

AC:

AN:

3438

East Asian (EAS)

AF:

0.000195

AC:

AN:

5124

South Asian (SAS)

AF:

0.00105

AC:

AN:

4768

European-Finnish (FIN)

AF:

0.000101

AC:

AN:

9920

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00116

AC:

AN:

67122

Other (OTH)

AF:

0.0524

AC:

108

AN:

2060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

348

696

1045

1393

1741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<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:

0.000288

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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