rs36210101

chr19-55133961-GGTGGGGAC-Gchr19-55133961-GGTGGGGAC-GGTGGGGACGTGGGGAC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_003283.6(TNNT1):c.751-42_751-35del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0438 in 1,613,074 control chromosomes in the GnomAD database, including 5,458 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (2368 hom., cov: 28)
  • Exomes 𝑓: 0.036 (3090 hom.)
• Consequence: TNNT1 NM_003283.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.113

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 -16 ACMG points.

• BP6: Variant 19-55133961-GGTGGGGAC-G is Benign according to our data. Variant chr19-55133961-GGTGGGGAC-G is described in ClinVar as [Benign]. Clinvar id is 259034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNNT1	NM_003283.6	c.751-42_751-35del		intron_variant		ENST00000588981.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNNT1	ENST00000588981.6	c.751-42_751-35del		intron_variant		1	NM_003283.6

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18063 AN: 151904 Hom.: 2356 Cov.: 28

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0186

Gnomad FIN AF: 0.0346

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0223

Gnomad OTH AF: 0.0998

GnomAD3 exomes AF: 0.0631 AC: 15731 AN: 249490 Hom.: 1256 AF XY: 0.0525 AC XY: 7105 AN XY: 135308

Gnomad AFR exome AF: 0.328

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.0162

Gnomad EAS exome AF: 0.119

Gnomad SAS exome AF: 0.0135

Gnomad FIN exome AF: 0.0323

Gnomad NFE exome AF: 0.0233

Gnomad OTH exome AF: 0.0493

GnomAD4 exome AF: 0.0359 AC: 52522 AN: 1461050 Hom.: 3090 AF XY: 0.0338 AC XY: 24553 AN XY: 726794

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.119

Gnomad4 ASJ exome AF: 0.0150

Gnomad4 EAS exome AF: 0.134

Gnomad4 SAS exome AF: 0.0132

Gnomad4 FIN exome AF: 0.0305

Gnomad4 NFE exome AF: 0.0220

Gnomad4 OTH exome AF: 0.0493

GnomAD4 genome AF: 0.119 AC: 18110 AN: 152024 Hom.: 2368 Cov.: 28 AF XY: 0.118 AC XY: 8766 AN XY: 74356

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.0186

Gnomad4 FIN AF: 0.0346

Gnomad4 NFE AF: 0.0223

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0181 Hom.: 21

Bravo AF: 0.136

Asia WGS AF: 0.107 AC: 372 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs36210101; hg19: chr19-55645329;