Variant 19-55132755-G-C 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_003283.6(TNNT1):c.*160C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 698,570 control chromosomes in the GnomAD database, including 28,041 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5643 hom., cov: 31)

Exomes 𝑓: 0.28 ( 22398 hom. )

Consequence

TNNT1
NM_003283.6 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0200

Variant links:

Genes affected

TNNT1 (HGNC:11948): (troponin T1, slow skeletal type) This gene encodes a protein that is a subunit of troponin, which is a regulatory complex located on the thin filament of the sarcomere. This complex regulates striated muscle contraction in response to fluctuations in intracellular calcium concentration. This complex is composed of three subunits: troponin C, which binds calcium, troponin T, which binds tropomyosin, and troponin I, which is an inhibitory subunit. This protein is the slow skeletal troponin T subunit. Mutations in this gene cause nemaline myopathy type 5, also known as Amish nemaline myopathy, a neuromuscular disorder characterized by muscle weakness and rod-shaped, or nemaline, inclusions in skeletal muscle fibers which affects infants, resulting in death due to respiratory insufficiency, usually in the second year. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

TNNT1 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=-0.88).

BP6

Variant 19-55132755-G-C is Benign according to our data. Variant chr19-55132755-G-C is described in ClinVar as [Benign]. Clinvar id is 1177785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNNT1	NM_003283.6 linkuse as main transcript	c.*160C>G		3_prime_UTR_variant	14/14	ENST00000588981.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNNT1	ENST00000588981.6 linkuse as main transcript	c.*160C>G		3_prime_UTR_variant	14/14	1	NM_003283.6		P13805-1

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41203

AN:

151962

Hom.:

5629

Cov.:

show subpopulations

Gnomad AFR

AF:

0.278

Gnomad AMI

AF:

0.234

Gnomad AMR

AF:

0.271

Gnomad ASJ

AF:

0.298

Gnomad EAS

AF:

0.362

Gnomad SAS

AF:

0.430

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.243

Gnomad OTH

AF:

0.282

GnomAD4 exome

AF:

0.277

AC:

151479

AN:

546488

Hom.:

22398

Cov.:

AF XY:

0.284

AC XY:

82362

AN XY:

289974

show subpopulations

Gnomad4 AFR exome

AF:

0.280

Gnomad4 AMR exome

AF:

0.295

Gnomad4 ASJ exome

AF:

0.300

Gnomad4 EAS exome

AF:

0.367

Gnomad4 SAS exome

AF:

0.417

Gnomad4 FIN exome

AF:

0.294

Gnomad4 NFE exome

AF:

0.240

Gnomad4 OTH exome

AF:

0.276

GnomAD4 genome

AF:

0.271

AC:

41244

AN:

152082

Hom.:

5643

Cov.:

AF XY:

0.277

AC XY:

20587

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.278

Gnomad4 AMR

AF:

0.271

Gnomad4 ASJ

AF:

0.298

Gnomad4 EAS

AF:

0.362

Gnomad4 SAS

AF:

0.431

Gnomad4 FIN

AF:

0.296

Gnomad4 NFE

AF:

0.243

Gnomad4 OTH

AF:

0.282

Alfa

AF:

0.253

Hom.:

641

Bravo

AF:

0.264

Asia WGS

AF:

0.359

AC:

1246

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.80

DANN

Benign

0.39

Splicing

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