Variant 14-91783156-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001128596.3(TC2N):c.1417A>G(p.Thr473Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

TC2N
NM_001128596.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.01

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34915793).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TC2N	NM_001128596.3 linkuse as main transcript	c.1417A>G	p.Thr473Ala	missense_variant	12/12	ENST00000435962.7	NP_001122068.2
TC2N	NM_001128595.3 linkuse as main transcript	c.1417A>G	p.Thr473Ala	missense_variant	12/12		NP_001122067.2
TC2N	NM_152332.6 linkuse as main transcript	c.1417A>G	p.Thr473Ala	missense_variant	12/12		NP_689545.2
TC2N	NM_001289134.2 linkuse as main transcript	c.1225A>G	p.Thr409Ala	missense_variant	11/11		NP_001276063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TC2N	ENST00000435962.7 linkuse as main transcript	c.1417A>G	p.Thr473Ala	missense_variant	12/12	2	NM_001128596.3	ENSP00000387882	P1	Q8N9U0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

250862

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135616

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460104

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726420

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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 03, 2023

The c.1417A>G (p.T473A) alteration is located in exon 12 (coding exon 11) of the TC2N gene. This alteration results from a A to G substitution at nucleotide position 1417, causing the threonine (T) at amino acid position 473 to be replaced by an alanine (A). 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

0.17

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.036

T;T;T;.;.

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.89

M_CAP

Benign

0.0078

MetaRNN

Benign

0.35

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L;L;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.2

N;N;N;N;N

REVEL

Benign

0.17

Sift

Uncertain

0.026

D;D;D;T;T

Sift4G

Benign

0.34

T;T;T;T;T

Polyphen

0.61

P;P;P;D;.

Vest4

0.19

MutPred

0.79

Gain of MoRF binding (P = 0.0864);Gain of MoRF binding (P = 0.0864);Gain of MoRF binding (P = 0.0864);.;.;

MVP

0.30

MPC

0.048

ClinPred

0.35

GERP RS

5.6

Varity_R

0.19

gMVP

0.38

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