Genetic Variant NM_003285.3:c.3237T>A (chr1-175355515-A-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_003285.3(TNR):c.3237T>A(p.Asp1079Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1079N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

TNR
NM_003285.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.951

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.802

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNR	NM_003285.3 link	c.3237T>A	p.Asp1079Glu	missense_variant	Exon 17 of 23	ENST00000367674.7	NP_003276.3	Q92752-1A1L306
TNR	NM_001328635.2 link	c.2238T>A	p.Asp746Glu	missense_variant	Exon 17 of 23		NP_001315564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNR	ENST00000367674.7 link	c.3237T>A	p.Asp1079Glu	missense_variant	Exon 17 of 23	5	NM_003285.3	ENSP00000356646.1	Q92752-1
TNR	ENST00000713954.1 link	c.3237T>A	p.Asp1079Glu	missense_variant	Exon 15 of 20			ENSP00000519247.1
TNR	ENST00000713977.1 link	c.2496T>A	p.Asp832Glu	missense_variant	Exon 14 of 20			ENSP00000519268.1
TNR	ENST00000713955.1 link	n.3237T>A		non_coding_transcript_exon_variant	Exon 15 of 21			ENSP00000519248.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152002

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152002

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74230

African (AFR)

AF:

0.00

AC:

AN:

41344

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2088

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

T;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.42

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

.;D

M_CAP

Benign

0.043

MetaRNN

Pathogenic

0.80

D;D

MetaSVM

Benign

-0.59

MutationAssessor

Uncertain

2.0

M;M

PhyloP100

0.95

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.7

D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.99

D;D

Vest4

0.46

MutPred

0.55

Loss of ubiquitination at K1076 (P = 0.0637);Loss of ubiquitination at K1076 (P = 0.0637);

MVP

0.51

MPC

0.75

ClinPred

0.99

GERP RS

0.15

Varity_R

0.44

gMVP

0.60

Mutation Taster

=74/26

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over