Variant 14-91798336-T-G 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.701A>C(p.Asn234Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000765 in 1,594,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

TC2N
NM_001128596.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.36

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=0.18526265).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TC2N	NM_001128596.3 linkuse as main transcript	c.701A>C	p.Asn234Thr	missense_variant	7/12	ENST00000435962.7	NP_001122068.2
TC2N	NM_001128595.3 linkuse as main transcript	c.701A>C	p.Asn234Thr	missense_variant	7/12		NP_001122067.2
TC2N	NM_152332.6 linkuse as main transcript	c.701A>C	p.Asn234Thr	missense_variant	7/12		NP_689545.2
TC2N	NM_001289134.2 linkuse as main transcript	c.701A>C	p.Asn234Thr	missense_variant	7/11		NP_001276063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TC2N	ENST00000435962.7 linkuse as main transcript	c.701A>C	p.Asn234Thr	missense_variant	7/12	2	NM_001128596.3	ENSP00000387882	P1	Q8N9U0-1

Frequencies

GnomAD3 genomes

AF:

0.0000724

AC:

AN:

151976

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:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000824

AC:

AN:

242692

Hom.:

AF XY:

0.0000836

AC XY:

AN XY:

131588

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:

0.0000465

Gnomad NFE exome

AF:

0.000171

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000770

AC:

111

AN:

1442148

Hom.:

Cov.:

AF XY:

0.0000640

AC XY:

AN XY:

718198

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:

0.0000375

Gnomad4 NFE exome

AF:

0.0000918

Gnomad4 OTH exome

AF:

0.000134

GnomAD4 genome

AF:

0.0000724

AC:

AN:

151976

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74216

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:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000822

Hom.:

Bravo

AF:

0.0000604

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000107

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

Sep 17, 2021

The c.701A>C (p.N234T) alteration is located in exon 7 (coding exon 6) of the TC2N gene. This alteration results from a A to C substitution at nucleotide position 701, causing the asparagine (N) at amino acid position 234 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

0.15

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.17

T;T;T;.;.

Eigen

Benign

-0.20

Eigen_PC

Benign

0.00029

FATHMM_MKL

Uncertain

0.80

M_CAP

Benign

0.014

MetaRNN

Benign

0.19

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.1

L;L;L;L;.

MutationTaster

Benign

0.97

N;N;N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-2.2

N;N;N;N;N

REVEL

Benign

0.16

Sift

Benign

0.22

T;T;T;T;T

Sift4G

Benign

0.76

T;T;T;T;T

Polyphen

0.26

B;B;B;B;.

Vest4

0.36

MVP

0.78

MPC

0.051

ClinPred

0.080

GERP RS

4.4

Varity_R

0.095

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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