Variant 1-175079444-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_022093.2(TNN):c.521C>T(p.Ala174Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,425,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

TNN
NM_022093.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00200

Variant links:

Genes affected

TNN (HGNC:22942): (tenascin N) Predicted to enable integrin binding activity. Predicted to be involved in several processes, including generation of neurons; negative regulation of canonical Wnt signaling pathway involved in osteoblast differentiation; and negative regulation of osteoblast differentiation. Predicted to act upstream of or within axonogenesis. Predicted to be located in extracellular matrix and neuron projection. Predicted to be active in collagen-containing extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

TNN 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=0.36258715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TNN	NM_022093.2 linkuse as main transcript	c.521C>T	p.Ala174Val	missense_variant	3/19	ENST00000239462.9	NP_071376.1
TNN	XM_017002048.2 linkuse as main transcript	c.575C>T	p.Ala192Val	missense_variant	3/19		XP_016857537.1
TNN	XM_017002049.2 linkuse as main transcript	c.575C>T	p.Ala192Val	missense_variant	3/18		XP_016857538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNN	ENST00000239462.9 linkuse as main transcript	c.521C>T	p.Ala174Val	missense_variant	3/19	2	NM_022093.2	ENSP00000239462	P1
TNN	ENST00000621086.1 linkuse as main transcript	c.521C>T	p.Ala174Val	missense_variant	2/16	5		ENSP00000480895

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000553

AC:

AN:

180862

Hom.:

AF XY:

0.00000998

AC XY:

AN XY:

100204

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:

0.0000818

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.02e-7

AC:

AN:

1425148

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

706940

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:

0.0000224

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 25, 2023

The c.521C>T (p.A174V) alteration is located in exon 3 (coding exon 2) of the TNN gene. This alteration results from a C to T substitution at nucleotide position 521, causing the alanine (A) at amino acid position 174 to be replaced by a valine (V). 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

0.091

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0046

T;.;.

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.10

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.36

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.8

M;.;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.9

N;.;.

REVEL

Benign

0.078

Sift

Benign

0.032

D;.;.

Sift4G

Benign

0.12

T;T;T

Polyphen

0.79

P;.;.

Vest4

0.34

MutPred

0.29

Loss of glycosylation at S176 (P = 0.2275);Loss of glycosylation at S176 (P = 0.2275);Loss of glycosylation at S176 (P = 0.2275);

MVP

0.47

MPC

0.12

ClinPred

0.30

GERP RS

3.5

Varity_R

0.067

gMVP

0.36

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