Variant 14-91802296-G-A 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.427C>T(p.Arg143Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000749 in 1,602,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R143H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000078 ( 0 hom. )

Consequence

TC2N
NM_001128596.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.40

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=0.1752151).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TC2N	NM_001128596.3 linkuse as main transcript	c.427C>T	p.Arg143Cys	missense_variant	4/12	ENST00000435962.7
TC2N	NM_001128595.3 linkuse as main transcript	c.427C>T	p.Arg143Cys	missense_variant	4/12
TC2N	NM_152332.6 linkuse as main transcript	c.427C>T	p.Arg143Cys	missense_variant	4/12
TC2N	NM_001289134.2 linkuse as main transcript	c.427C>T	p.Arg143Cys	missense_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TC2N	ENST00000435962.7 linkuse as main transcript	c.427C>T	p.Arg143Cys	missense_variant	4/12	2	NM_001128596.3	P1	Q8N9U0-1
TC2N	ENST00000340892.9 linkuse as main transcript	c.427C>T	p.Arg143Cys	missense_variant	4/12	1		P1	Q8N9U0-1
TC2N	ENST00000360594.9 linkuse as main transcript	c.427C>T	p.Arg143Cys	missense_variant	4/12	1		P1	Q8N9U0-1
TC2N	ENST00000556018.5 linkuse as main transcript	c.427C>T	p.Arg143Cys	missense_variant	4/11	2			Q8N9U0-2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000627

AC:

AN:

239360

Hom.:

AF XY:

0.0000540

AC XY:

AN XY:

129566

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000136

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000779

AC:

113

AN:

1450054

Hom.:

Cov.:

AF XY:

0.0000680

AC XY:

AN XY:

721044

show subpopulations

Gnomad4 AFR exome

AF:

0.0000917

Gnomad4 AMR exome

AF:

0.0000473

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000912

Gnomad4 OTH exome

AF:

0.0000834

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000141

Hom.:

Bravo

AF:

0.0000567

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000988

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

Feb 28, 2023

The c.427C>T (p.R143C) alteration is located in exon 4 (coding exon 3) of the TC2N gene. This alteration results from a C to T substitution at nucleotide position 427, causing the arginine (R) at amino acid position 143 to be replaced by a cysteine (C). 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

0.096

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

T;T;T;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.064

FATHMM_MKL

Uncertain

0.87

M_CAP

Benign

0.017

MetaRNN

Benign

0.18

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M;M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.9

N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.066

T;T;T;T

Sift4G

Benign

0.14

T;T;T;T

Polyphen

0.10

B;B;B;B

Vest4

0.32

MVP

0.40

MPC

0.076

ClinPred

0.30

GERP RS

4.7

Varity_R

0.11

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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