1-201368042-A-G

Position:

• chr1-201368042-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001276345.2(TNNT2):​c.163+120T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 1,100,764 control chromosomes in the GnomAD database, including 383,301 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.84 (54091 hom., cov: 31)
  • Exomes 𝑓: 0.83 (329210 hom.)
• Consequence: TNNT2 NM_001276345.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.157

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-201368042-A-G is Benign according to our data. Variant chr1-201368042-A-G is described in ClinVar as [Benign]. Clinvar id is 671945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-201368042-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNNT2	NM_001276345.2	c.163+120T>C		intron_variant		ENST00000656932.1	NP_001263274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNNT2	ENST00000656932.1	c.163+120T>C		intron_variant			NM_001276345.2	ENSP00000499593	A2

Frequencies

GnomAD3 genomes AF: 0.843 AC: 128076 AN: 151986 Hom.: 54035 Cov.: 31

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.894

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.831

GnomAD4 exome AF: 0.832 AC: 789657 AN: 948658 Hom.: 329210 AF XY: 0.835 AC XY: 412073 AN XY: 493778

Gnomad4 AFR exome AF: 0.863

Gnomad4 AMR exome AF: 0.893

Gnomad4 ASJ exome AF: 0.852

Gnomad4 EAS exome AF: 0.818

Gnomad4 SAS exome AF: 0.891

Gnomad4 FIN exome AF: 0.872

Gnomad4 NFE exome AF: 0.817

Gnomad4 OTH exome AF: 0.840

GnomAD4 genome AF: 0.843 AC: 128196 AN: 152106 Hom.: 54091 Cov.: 31 AF XY: 0.847 AC XY: 62962 AN XY: 74368

Gnomad4 AFR AF: 0.861

Gnomad4 AMR AF: 0.870

Gnomad4 ASJ AF: 0.862

Gnomad4 EAS AF: 0.829

Gnomad4 SAS AF: 0.893

Gnomad4 FIN AF: 0.880

Gnomad4 NFE AF: 0.819

Gnomad4 OTH AF: 0.833

Alfa AF: 0.819 Hom.: 7983

Bravo AF: 0.840

Asia WGS AF: 0.880 AC: 3061 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Dilated cardiomyopathy 1D Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Cardiomyopathy, familial restrictive, 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Hypertrophic cardiomyopathy 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Dilated cardiomyopathy 1D;C1861864:Hypertrophic cardiomyopathy 2;C2676271:Cardiomyopathy, familial restrictive, 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.40

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

Other links and lift over

dbSNP: rs3729842; hg19: chr1-201337170;