Variant 14-91792447-C-T 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.967G>A(p.Glu323Lys) 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 1,459,150 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 1 hom. )

Consequence

TC2N
NM_001128596.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.19

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:

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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=0.29056978).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TC2N	NM_001128596.3 linkuse as main transcript	c.967G>A	p.Glu323Lys	missense_variant	9/12	ENST00000435962.7	NP_001122068.2	Q8N9U0-1
TC2N	NM_001128595.3 linkuse as main transcript	c.967G>A	p.Glu323Lys	missense_variant	9/12		NP_001122067.2	Q8N9U0-1
TC2N	NM_152332.6 linkuse as main transcript	c.967G>A	p.Glu323Lys	missense_variant	9/12		NP_689545.2	Q8N9U0-1
TC2N	NM_001289134.2 linkuse as main transcript	c.856-4820G>A		intron_variant			NP_001276063.2	Q8N9U0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TC2N	ENST00000435962.7 linkuse as main transcript	c.967G>A	p.Glu323Lys	missense_variant	9/12	2	NM_001128596.3	ENSP00000387882.2		Q8N9U0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1459150

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725888

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:

0.0000349

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 01, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

T;T;T;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.56

FATHMM_MKL

Uncertain

0.85

M_CAP

Benign

0.054

MetaRNN

Benign

0.29

T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.4

M;M;M;.

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.3

D;D;D;D

REVEL

Benign

0.22

Sift

Benign

0.041

D;D;D;D

Sift4G

Uncertain

0.019

D;D;D;D

Polyphen

0.013

B;B;B;.

Vest4

0.37

MutPred

0.57

Gain of MoRF binding (P = 0.0018);Gain of MoRF binding (P = 0.0018);Gain of MoRF binding (P = 0.0018);.;

MVP

0.66

MPC

0.074

ClinPred

0.96

GERP RS

2.8

Varity_R

0.23

gMVP

0.70

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