1-201362426-T-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001276345.2(TNNT2):c.601-32A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 1,611,296 control chromosomes in the GnomAD database, including 422,566 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.74 ( 41807 hom., cov: 32)

Exomes 𝑓: 0.72 ( 380759 hom. )

Consequence

TNNT2
NM_001276345.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.21

Variant links:

Genes affected

TNNT2 (HGNC:11949): (troponin T2, cardiac type) This gene encodes the cardiac isoform of troponin T. The encoded protein is the tropomyosin-binding subunit of the troponin complex, which is located on the thin filament of striated muscles and regulates muscle contraction in response to alterations in intracellular calcium ion concentration. Mutations in this gene have been associated with familial hypertrophic cardiomyopathy as well as with dilated cardiomyopathy. [provided by RefSeq, May 2022]

TNNT2 links:

ENSG00000286600 (HGNC:):

ENSG00000286600 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 1-201362426-T-G is Benign according to our data. Variant chr1-201362426-T-G is described in ClinVar as [Benign]. Clinvar id is 256845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-201362426-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNNT2	NM_001276345.2 link	c.601-32A>C		intron_variant	Intron 12 of 16	ENST00000656932.1	NP_001263274.1	P45379-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNNT2	ENST00000656932.1 link	c.601-32A>C		intron_variant	Intron 12 of 16		NM_001276345.2	ENSP00000499593.1		P45379-1

Frequencies

GnomAD3 genomes

AF:

0.741

AC:

112517

AN:

151940

Hom.:

41769

Cov.:

show subpopulations

Gnomad AFR

AF:

0.766

Gnomad AMI

AF:

0.605

Gnomad AMR

AF:

0.767

Gnomad ASJ

AF:

0.782

Gnomad EAS

AF:

0.558

Gnomad SAS

AF:

0.822

Gnomad FIN

AF:

0.802

Gnomad MID

AF:

0.763

Gnomad NFE

AF:

0.717

Gnomad OTH

AF:

0.730

GnomAD3 exomes

AF:

0.735

AC:

180715

AN:

245982

Hom.:

66911

AF XY:

0.739

AC XY:

98251

AN XY:

133028

show subpopulations

Gnomad AFR exome

AF:

0.766

Gnomad AMR exome

AF:

0.773

Gnomad ASJ exome

AF:

0.773

Gnomad EAS exome

AF:

0.545

Gnomad SAS exome

AF:

0.825

Gnomad FIN exome

AF:

0.789

Gnomad NFE exome

AF:

0.710

Gnomad OTH exome

AF:

0.754

GnomAD4 exome

AF:

0.721

AC:

1051935

AN:

1459238

Hom.:

380759

Cov.:

AF XY:

0.725

AC XY:

525962

AN XY:

725692

show subpopulations

Gnomad4 AFR exome

AF:

0.766

Gnomad4 AMR exome

AF:

0.773

Gnomad4 ASJ exome

AF:

0.778

Gnomad4 EAS exome

AF:

0.580

Gnomad4 SAS exome

AF:

0.821

Gnomad4 FIN exome

AF:

0.791

Gnomad4 NFE exome

AF:

0.709

Gnomad4 OTH exome

AF:

0.735

GnomAD4 genome

AF:

0.741

AC:

112611

AN:

152058

Hom.:

41807

Cov.:

AF XY:

0.745

AC XY:

55411

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.766

Gnomad4 AMR

AF:

0.768

Gnomad4 ASJ

AF:

0.782

Gnomad4 EAS

AF:

0.558

Gnomad4 SAS

AF:

0.821

Gnomad4 FIN

AF:

0.802

Gnomad4 NFE

AF:

0.717

Gnomad4 OTH

AF:

0.730

Alfa

AF:

0.736

Hom.:

9050

Bravo

AF:

0.734

Asia WGS

AF:

0.687

AC:

2390

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypertrophic cardiomyopathy 2

Benign:2

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dilated cardiomyopathy 1D

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiomyopathy, familial restrictive, 3

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.85

La Branchor

0.71

BranchPoint Hunter

3.0

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