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GeneBe

1-201362426-T-G

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 (★★).

Frequency

Genomes: 𝑓 0.74 ( 41807 hom., cov: 32)
Exomes 𝑓: 0.72 ( 380759 hom. )

Consequence

TNNT2
NM_001276345.2 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4
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/exons MANE UniProt
TNNT2NM_001276345.2 linkuse as main transcriptc.601-32A>C intron_variant ENST00000656932.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TNNT2ENST00000656932.1 linkuse as main transcriptc.601-32A>C intron_variant NM_001276345.2 A2P45379-1

Frequencies

GnomAD3 genomes
AF:
0.741
AC:
112517
AN:
151940
Hom.:
41769
Cov.:
32
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.:
40
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.:
32
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:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Hypertrophic cardiomyopathy 2 Benign:2
Benign, criteria provided, single submitterclinical testingMendelicsMay 28, 2019- -
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 10, 2021- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Dilated cardiomyopathy 1D Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 10, 2021- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -
Cardiomyopathy, familial restrictive, 3 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 10, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.40
Cadd
Benign
17
Dann
Benign
0.85
La Branchor
0.71

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.

Other links and lift over

dbSNP: rs1104859; hg19: chr1-201331554; COSMIC: COSV52662302; COSMIC: COSV52662302; API