Variant chr20-45824114-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM1BS2

The NM_003279.3(TNNC2):c.328T>C(p.Tyr110His) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,613,608 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

TNNC2
NM_003279.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.98

Variant links:

Genes affected

TNNC2 (HGNC:11944): (troponin C2, fast skeletal type) Troponin (Tn), a key protein complex in the regulation of striated muscle contraction, is composed of 3 subunits. The Tn-I subunit inhibits actomyosin ATPase, the Tn-T subunit binds tropomyosin and Tn-C, while the Tn-C subunit binds calcium and overcomes the inhibitory action of the troponin complex on actin filaments. The protein encoded by this gene is the Tn-C subunit. [provided by RefSeq, Jul 2008]

TNNC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity TNNC2_HUMAN

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNNC2	NM_003279.3 linkuse as main transcript	c.328T>C	p.Tyr110His	missense_variant	5/6	ENST00000372555.8	NP_003270.1	P02585
TNNC2	XM_011529031.3 linkuse as main transcript	c.283T>C	p.Tyr95His	missense_variant	5/6		XP_011527333.1	C9J7T9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNNC2	ENST00000372555.8 linkuse as main transcript	c.328T>C	p.Tyr110His	missense_variant	5/6	1	NM_003279.3	ENSP00000361636.3		P02585
TNNC2	ENST00000372557.1 linkuse as main transcript	c.283T>C	p.Tyr95His	missense_variant	6/7	3		ENSP00000361638.1		C9J7T9

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151922

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

250894

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135614

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000398

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461686

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151922

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000451

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 30, 2024

The c.328T>C (p.Y110H) alteration is located in exon 5 (coding exon 5) of the TNNC2 gene. This alteration results from a T to C substitution at nucleotide position 328, causing the tyrosine (Y) at amino acid position 110 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Uncertain

0.070

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.75

D;.

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.97

D;D

M_CAP

Uncertain

0.21

MetaRNN

Uncertain

0.47

T;T

MetaSVM

Benign

-0.28

MutationAssessor

Benign

1.9

L;.

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.4

D;D

REVEL

Uncertain

0.49

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.071

T;T

Polyphen

0.92

P;.

Vest4

0.54

MutPred

0.37

Gain of disorder (P = 0.0154);.;

MVP

0.43

MPC

1.9

ClinPred

0.81

GERP RS

4.1

Varity_R

0.76

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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