Variant chr14-91799060-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001128596.3(TC2N):c.566A>G(p.His189Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000159 in 1,571,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000099 ( 0 hom. )

Consequence

TC2N
NM_001128596.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.20

Variant links:

Genes affected

TC2N (HGNC:19859): (tandem C2 domains, nuclear) Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TC2N links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10298124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TC2N	NM_001128596.3 linkuse as main transcript	c.566A>G	p.His189Arg	missense_variant	6/12	ENST00000435962.7	NP_001122068.2	Q8N9U0-1
TC2N	NM_001128595.3 linkuse as main transcript	c.566A>G	p.His189Arg	missense_variant	6/12		NP_001122067.2	Q8N9U0-1
TC2N	NM_152332.6 linkuse as main transcript	c.566A>G	p.His189Arg	missense_variant	6/12		NP_689545.2	Q8N9U0-1
TC2N	NM_001289134.2 linkuse as main transcript	c.566A>G	p.His189Arg	missense_variant	6/11		NP_001276063.2	Q8N9U0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TC2N	ENST00000435962.7 linkuse as main transcript	c.566A>G	p.His189Arg	missense_variant	6/12	2	NM_001128596.3	ENSP00000387882.2	Q8N9U0-1
TC2N	ENST00000340892.9 linkuse as main transcript	c.566A>G	p.His189Arg	missense_variant	6/12	1		ENSP00000343199.5	Q8N9U0-1
TC2N	ENST00000360594.9 linkuse as main transcript	c.566A>G	p.His189Arg	missense_variant	6/12	1		ENSP00000353802.5	Q8N9U0-1
TC2N	ENST00000556018.5 linkuse as main transcript	c.566A>G	p.His189Arg	missense_variant	6/11	2		ENSP00000451317.1	Q8N9U0-2

Frequencies

GnomAD3 genomes

AF:

0.0000724

AC:

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000323

AC:

AN:

216722

Hom.:

AF XY:

0.0000423

AC XY:

AN XY:

118196

show subpopulations

Gnomad AFR exome

AF:

0.000141

Gnomad AMR exome

AF:

0.0000810

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000193

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:

0.00000986

AC:

AN:

1419264

Hom.:

Cov.:

AF XY:

0.0000156

AC XY:

AN XY:

706514

show subpopulations

Gnomad4 AFR exome

AF:

0.0000657

Gnomad4 AMR exome

AF:

0.0000591

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000259

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000822

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000278

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000494

AC:

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 21, 2024

The c.566A>G (p.H189R) alteration is located in exon 6 (coding exon 5) of the TC2N gene. This alteration results from a A to G substitution at nucleotide position 566, causing the histidine (H) at amino acid position 189 to be replaced by an arginine (R). 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

Benign

0.093

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.043

T;T;T;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.091

FATHMM_MKL

Uncertain

0.94

M_CAP

Benign

0.0083

MetaRNN

Benign

0.10

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;M;M;M

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.5

N;N;N;N

REVEL

Benign

0.040

Sift

Uncertain

0.0080

D;D;D;D

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.090

B;B;B;B

Vest4

0.29

MVP

0.28

MPC

0.053

ClinPred

0.073

GERP RS

4.2

Varity_R

0.12

gMVP

0.27

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