Variant chr14-91797786-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001128596.3(TC2N):c.854A>G(p.Asn285Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000495 in 1,575,570 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000051 ( 1 hom. )

Consequence

TC2N
NM_001128596.3 missense, splice_region

Scores

Splicing: ADA: 0.03586

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.92

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009287566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TC2N	NM_001128596.3 linkuse as main transcript	c.854A>G	p.Asn285Ser	missense_variant, splice_region_variant	8/12	ENST00000435962.7
TC2N	NM_001128595.3 linkuse as main transcript	c.854A>G	p.Asn285Ser	missense_variant, splice_region_variant	8/12
TC2N	NM_152332.6 linkuse as main transcript	c.854A>G	p.Asn285Ser	missense_variant, splice_region_variant	8/12
TC2N	NM_001289134.2 linkuse as main transcript	c.854A>G	p.Asn285Ser	missense_variant, splice_region_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TC2N	ENST00000435962.7 linkuse as main transcript	c.854A>G	p.Asn285Ser	missense_variant, splice_region_variant	8/12	2	NM_001128596.3	P1	Q8N9U0-1

Frequencies

GnomAD3 genomes

AF:

0.0000396

AC:

AN:

151514

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000821

AC:

AN:

231508

Hom.:

AF XY:

0.0000719

AC XY:

AN XY:

125232

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:

0.000748

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000506

AC:

AN:

1423944

Hom.:

Cov.:

AF XY:

0.0000606

AC XY:

AN XY:

708994

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:

0.000758

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000367

Gnomad4 OTH exome

AF:

0.000119

GnomAD4 genome

AF:

0.0000396

AC:

AN:

151626

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74074

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000509

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000659

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 27, 2021

The c.854A>G (p.N285S) alteration is located in exon 8 (coding exon 7) of the TC2N gene. This alteration results from a A to G substitution at nucleotide position 854, causing the asparagine (N) at amino acid position 285 to be replaced by a serine (S). 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

0.056

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.47

DANN

Benign

0.46

DEOGEN2

Benign

0.032

T;T;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.036

M_CAP

Benign

0.018

MetaRNN

Benign

0.0083

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.035

N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.55

N;N;N;N

REVEL

Benign

0.034

Sift

Benign

0.13

T;T;T;T

Sift4G

Benign

0.71

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.13

MutPred

0.29

Gain of disorder (P = 0.0588);Gain of disorder (P = 0.0588);Gain of disorder (P = 0.0588);Gain of disorder (P = 0.0588);

MVP

0.29

MPC

0.040

ClinPred

0.011

GERP RS

-3.9

Varity_R

0.037

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.036

dbscSNV1_RF

Benign

0.40

SpliceAI score (max)

0.030

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