rs36210101

Variant names:

• chr19-55133961-GGTGGGGAC-G
• rs36210101
• NM_003283.6:c.751-42_751-35delGTCCCCAC

Your query was ambiguous. Multiple possible variants found:

• chr19-55133961-GGTGGGGAC-G
• chr19-55133961-GGTGGGGAC-GGTGGGGACGTGGGGAC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_003283.6(TNNT1):​c.751-42_751-35delGTCCCCAC 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
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• nemaline myopathy 5

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• nemaline myopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• nemaline myopathy 5C, autosomal dominant

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
TNNT1	NM_003283.6	c.751-42_751-35delGTCCCCAC		intron_variant	Intron 12 of 13	ENST00000588981.6	NP_003274.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNNT1	ENST00000588981.6	c.751-42_751-35delGTCCCCAC		intron_variant	Intron 12 of 13	1	NM_003283.6	ENSP00000467176.1

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

GnomAD2 exomes AF: 0.0631 AC: 15731 AN: 249490 AF XY: 0.0525

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 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

African (AFR) AF: 0.333 AC: 11155 AN: 33458

American (AMR) AF: 0.119 AC: 5331 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 393 AN: 26122

East Asian (EAS) AF: 0.134 AC: 5325 AN: 39686

South Asian (SAS) AF: 0.0132 AC: 1138 AN: 86232

European-Finnish (FIN) AF: 0.0305 AC: 1608 AN: 52780

Middle Eastern (MID) AF: 0.0319 AC: 184 AN: 5768

European-Non Finnish (NFE) AF: 0.0220 AC: 24413 AN: 1111932

Other (OTH) AF: 0.0493 AC: 2975 AN: 60380

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

African (AFR) AF: 0.324 AC: 13398 AN: 41348

American (AMR) AF: 0.122 AC: 1872 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0135 AC: 47 AN: 3470

East Asian (EAS) AF: 0.117 AC: 602 AN: 5152

South Asian (SAS) AF: 0.0186 AC: 90 AN: 4830

European-Finnish (FIN) AF: 0.0346 AC: 367 AN: 10610

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0223 AC: 1514 AN: 68002

Other (OTH) AF: 0.101 AC: 214 AN: 2116

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

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs36210101; hg19: chr19-55645329; COSMIC: COSV107342883; COSMIC: COSV107342883;