Variant chr11-1922972-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006757.4(TNNT3):c.18-76A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 1,613,150 control chromosomes in the GnomAD database, including 516,905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 43236 hom., cov: 32)

Exomes 𝑓: 0.80 ( 473669 hom. )

Consequence

TNNT3
NM_006757.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: -2.20

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 11-1922972-A-G is Benign according to our data. Variant chr11-1922972-A-G is described in ClinVar as [Benign]. Clinvar id is 31868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNNT3	NM_006757.4 linkuse as main transcript	c.18-76A>G		intron_variant		ENST00000278317.11	NP_006748.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNNT3	ENST00000278317.11 linkuse as main transcript	c.18-76A>G		intron_variant		5	NM_006757.4	ENSP00000278317	A2	P45378-2

Frequencies

GnomAD3 genomes

AF:

0.744

AC:

113028

AN:

151922

Hom.:

43225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.554

Gnomad AMI

AF:

0.807

Gnomad AMR

AF:

0.833

Gnomad ASJ

AF:

0.858

Gnomad EAS

AF:

0.927

Gnomad SAS

AF:

0.914

Gnomad FIN

AF:

0.766

Gnomad MID

AF:

0.864

Gnomad NFE

AF:

0.802

Gnomad OTH

AF:

0.771

GnomAD4 exome

AF:

0.803

AC:

1173479

AN:

1461110

Hom.:

473669

Cov.:

AF XY:

0.807

AC XY:

586961

AN XY:

726890

show subpopulations

Gnomad4 AFR exome

AF:

0.542

Gnomad4 AMR exome

AF:

0.879

Gnomad4 ASJ exome

AF:

0.852

Gnomad4 EAS exome

AF:

0.928

Gnomad4 SAS exome

AF:

0.912

Gnomad4 FIN exome

AF:

0.766

Gnomad4 NFE exome

AF:

0.795

Gnomad4 OTH exome

AF:

0.804

GnomAD4 genome

AF:

0.744

AC:

113084

AN:

152040

Hom.:

43236

Cov.:

AF XY:

0.748

AC XY:

55611

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.554

Gnomad4 AMR

AF:

0.834

Gnomad4 ASJ

AF:

0.858

Gnomad4 EAS

AF:

0.927

Gnomad4 SAS

AF:

0.915

Gnomad4 FIN

AF:

0.766

Gnomad4 NFE

AF:

0.802

Gnomad4 OTH

AF:

0.767

Alfa

AF:

0.790

Hom.:

27439

Bravo

AF:

0.737

Asia WGS

AF:

0.854

AC:

2968

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
not provided, no classification provided	curation	Leiden Muscular Dystrophy (TNNT3)	Mar 18, 2012	- -

Arthrogryposis, distal, type 2B2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.54

DANN

Benign

0.54

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

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