rs147204644

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_003285.3(TNR):c.496A>G(p.Thr166Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00468 in 1,613,638 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0040 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 22 hom. )

Consequence

TNR
NM_003285.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 3.79

Publications

9 publications found

Variant links:

Genes affected

TNR (HGNC:11953): (tenascin R) This gene encodes a member of the tenascin family of extracellular matrix glycoproteins. The encoded protein is restricted to the central nervous system. The protein may play a role in neurite outgrowth, neural cell adhesion and modulation of sodium channel function. It is a constituent of perineuronal nets. [provided by RefSeq, Aug 2013]

TNR Gene-Disease associations (from GenCC):

neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

TNR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010126919).

BP6

Variant 1-175406219-T-C is Benign according to our data. Variant chr1-175406219-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 224864.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00404 (615/152298) while in subpopulation AMR AF = 0.00595 (91/15302). AF 95% confidence interval is 0.00533. There are 2 homozygotes in GnomAd4. There are 288 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNR	NM_003285.3 link	c.496A>G	p.Thr166Ala	missense_variant	Exon 3 of 23	ENST00000367674.7	NP_003276.3	Q92752-1A1L306
TNR	NM_001328635.2 link	c.-400A>G		5_prime_UTR_variant	Exon 3 of 23		NP_001315564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNR	ENST00000367674.7 link	c.496A>G	p.Thr166Ala	missense_variant	Exon 3 of 23	5	NM_003285.3	ENSP00000356646.1		Q92752-1

Frequencies

GnomAD3 genomes

AF:

0.00405

AC:

616

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.00595

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.0287

Gnomad NFE

AF:

0.00581

Gnomad OTH

AF:

0.00718

GnomAD2 exomes

AF:

0.00428

AC:

1062

AN:

248350

AF XY:

0.00432

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00550

Gnomad ASJ exome

AF:

0.00997

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00241

Gnomad NFE exome

AF:

0.00568

Gnomad OTH exome

AF:

0.00573

GnomAD4 exome

AF:

0.00475

AC:

6938

AN:

1461340

Hom.:

Cov.:

AF XY:

0.00470

AC XY:

3419

AN XY:

726960

show subpopulations

African (AFR)

AF:

0.000807

AC:

AN:

33474

American (AMR)

AF:

0.00523

AC:

234

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00977

AC:

255

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00147

AC:

127

AN:

86184

European-Finnish (FIN)

AF:

0.00227

AC:

121

AN:

53372

Middle Eastern (MID)

AF:

0.0104

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00521

AC:

5795

AN:

1111664

Other (OTH)

AF:

0.00528

AC:

319

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

390

781

1171

1562

1952

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

216

432

648

864

1080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00404

AC:

615

AN:

152298

Hom.:

Cov.:

AF XY:

0.00387

AC XY:

288

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00103

AC:

AN:

41570

American (AMR)

AF:

0.00595

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00720

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00187

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00207

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0274

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00581

AC:

395

AN:

68024

Other (OTH)

AF:

0.00711

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

100

134

167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00470

Hom.:

Bravo

AF:

0.00453

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00558

AC:

ExAC

AF:

0.00435

AC:

528

EpiCase

AF:

0.00627

EpiControl

AF:

0.00563

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

TNR: BP4, BS2 -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Parkinson disease

Uncertain:1

Jan 01, 2016

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:research

- -

Inborn genetic diseases

Benign:1

Dec 28, 2021

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

0.067

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.32

T;T

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.84

.;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.3

L;L

PhyloP100

3.8

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.19

Sift

Benign

0.18

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.93

P;P

Vest4

0.27

MVP

0.50

MPC

0.21

ClinPred

0.022

GERP RS

5.1

PromoterAI

-0.0069

Neutral

(source)

Varity_R

0.19

gMVP

0.24

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over