Variant 14-91799031-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001128596.3(TC2N):c.595T>A(p.Ser199Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000595 in 1,597,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

TC2N
NM_001128596.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.21

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04335648).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TC2N	NM_001128596.3 linkuse as main transcript	c.595T>A	p.Ser199Thr	missense_variant	6/12	ENST00000435962.7	NP_001122068.2
TC2N	NM_001128595.3 linkuse as main transcript	c.595T>A	p.Ser199Thr	missense_variant	6/12		NP_001122067.2
TC2N	NM_152332.6 linkuse as main transcript	c.595T>A	p.Ser199Thr	missense_variant	6/12		NP_689545.2
TC2N	NM_001289134.2 linkuse as main transcript	c.595T>A	p.Ser199Thr	missense_variant	6/11		NP_001276063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TC2N	ENST00000435962.7 linkuse as main transcript	c.595T>A	p.Ser199Thr	missense_variant	6/12	2	NM_001128596.3	ENSP00000387882	P1	Q8N9U0-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000127

AC:

AN:

236208

Hom.:

AF XY:

0.0000234

AC XY:

AN XY:

128162

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:

0.0000184

Gnomad OTH exome

AF:

0.000173

GnomAD4 exome

AF:

0.0000636

AC:

AN:

1445882

Hom.:

Cov.:

AF XY:

0.0000667

AC XY:

AN XY:

719478

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000778

Gnomad4 OTH exome

AF:

0.0000838

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152010

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000442

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000849

Hom.:

ExAC

AF:

0.00000824

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

Jan 31, 2024

The c.595T>A (p.S199T) alteration is located in exon 6 (coding exon 5) of the TC2N gene. This alteration results from a T to A substitution at nucleotide position 595, causing the serine (S) at amino acid position 199 to be replaced by a threonine (T). 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

0.065

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.010

T;T;T;.

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.49

M_CAP

Benign

0.0038

MetaRNN

Benign

0.043

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.5

L;L;L;L

MutationTaster

Benign

0.89

N;N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.39

N;N;N;N

REVEL

Benign

0.031

Sift

Benign

0.22

T;T;T;T

Sift4G

Benign

0.53

T;T;T;T

Polyphen

0.0010

B;B;B;B

Vest4

0.18

MVP

0.17

MPC

0.043

ClinPred

0.041

GERP RS

-0.18

Varity_R

0.061

gMVP

0.28

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