19-55132755-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0200

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	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	c.*160C>G		3_prime_UTR_variant	14/14	1	NM_003283.6

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41203 AN: 151962 Hom.: 5629 Cov.: 31

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.: 6 AF XY: 0.284 AC XY: 82362 AN XY: 289974

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.: 31 AF XY: 0.277 AC XY: 20587 AN XY: 74342

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2018

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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

Other links and lift over

dbSNP: rs10414711; hg19: chr19-55644123; COSMIC: COSV52570335;