Variant 1-175077699-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_022093.2(TNN):c.281C>T(p.Thr94Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,614,192 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0097 ( 14 hom., cov: 32)

Exomes 𝑓: 0.012 ( 133 hom. )

Consequence

TNN
NM_022093.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.02

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007320255).

BP6

Variant 1-175077699-C-T is Benign according to our data. Variant chr1-175077699-C-T is described in ClinVar as [Benign]. Clinvar id is 3342247.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TNN	NM_022093.2 linkuse as main transcript	c.281C>T	p.Thr94Met	missense_variant	2/19	ENST00000239462.9	NP_071376.1
TNN	XM_017002048.2 linkuse as main transcript	c.335C>T	p.Thr112Met	missense_variant	2/19		XP_016857537.1
TNN	XM_017002049.2 linkuse as main transcript	c.335C>T	p.Thr112Met	missense_variant	2/18		XP_016857538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNN	ENST00000239462.9 linkuse as main transcript	c.281C>T	p.Thr94Met	missense_variant	2/19	2	NM_022093.2	ENSP00000239462	P1
TNN	ENST00000621086.1 linkuse as main transcript	c.281C>T	p.Thr94Met	missense_variant	1/16	5		ENSP00000480895

Frequencies

GnomAD3 genomes

AF:

0.00970

AC:

1477

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00244

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.00752

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00745

Gnomad FIN

AF:

0.0231

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0138

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00981

AC:

2465

AN:

251158

Hom.:

AF XY:

0.00993

AC XY:

1348

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.00216

Gnomad AMR exome

AF:

0.00602

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.00709

Gnomad FIN exome

AF:

0.0249

Gnomad NFE exome

AF:

0.0120

Gnomad OTH exome

AF:

0.0135

GnomAD4 exome

AF:

0.0121

AC:

17693

AN:

1461876

Hom.:

133

Cov.:

AF XY:

0.0121

AC XY:

8774

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00227

Gnomad4 AMR exome

AF:

0.00631

Gnomad4 ASJ exome

AF:

0.00168

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00699

Gnomad4 FIN exome

AF:

0.0229

Gnomad4 NFE exome

AF:

0.0133

Gnomad4 OTH exome

AF:

0.0102

GnomAD4 genome

AF:

0.00970

AC:

1477

AN:

152316

Hom.:

Cov.:

AF XY:

0.00992

AC XY:

739

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00243

Gnomad4 AMR

AF:

0.00751

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00745

Gnomad4 FIN

AF:

0.0231

Gnomad4 NFE

AF:

0.0138

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.0114

Hom.:

Bravo

AF:

0.00798

TwinsUK

AF:

0.0138

AC:

ALSPAC

AF:

0.0148

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0135

AC:

116

ExAC

AF:

0.00954

AC:

1158

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0118

EpiControl

AF:

0.0103

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

TNN: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.046

T;.;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.75

T;T;T

MetaRNN

Benign

0.0073

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

M;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.6

D;.;.

REVEL

Benign

0.13

Sift

Benign

0.14

T;.;.

Sift4G

Uncertain

0.0070

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.35

MPC

0.11

ClinPred

0.033

GERP RS

5.5

Varity_R

0.079

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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