Genetic Variant NM_003285.3:c.2054-138T>G (chr1-175366276-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003285.3(TNR):c.2054-138T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 885,400 control chromosomes in the GnomAD database, including 275,497 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.80 ( 48552 hom., cov: 33)

Exomes 𝑓: 0.78 ( 226945 hom. )

Consequence

TNR
NM_003285.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.712

Publications

10 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: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia

TNR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003285.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNR	NM_003285.3	MANE Select	c.2054-138T>G		intron	N/A	NP_003276.3
	TNR	NM_001328635.2		c.1055-138T>G		intron	N/A	NP_001315564.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNR	ENST00000367674.7	TSL:5 MANE Select	c.2054-138T>G	intron	N/A	ENSP00000356646.1	Q92752-1
TNR	ENST00000713954.1		c.2054-138T>G	intron	N/A	ENSP00000519247.1	A0AAQ5BH57
TNR	ENST00000713977.1		c.1313-138T>G	intron	N/A	ENSP00000519268.1	A0AAQ5BHB2

Frequencies

GnomAD3 genomes

AF:

0.798

AC:

121293

AN:

152068

Hom.:

48504

Cov.:

show subpopulations

Gnomad AFR

AF:

0.835

Gnomad AMI

AF:

0.720

Gnomad AMR

AF:

0.818

Gnomad ASJ

AF:

0.749

Gnomad EAS

AF:

0.808

Gnomad SAS

AF:

0.732

Gnomad FIN

AF:

0.823

Gnomad MID

AF:

0.734

Gnomad NFE

AF:

0.774

Gnomad OTH

AF:

0.789

GnomAD4 exome

AF:

0.784

AC:

575066

AN:

733214

Hom.:

226945

AF XY:

0.783

AC XY:

285984

AN XY:

365118

show subpopulations

African (AFR)

AF:

0.843

AC:

14687

AN:

17426

American (AMR)

AF:

0.826

AC:

13272

AN:

16072

Ashkenazi Jewish (ASJ)

AF:

0.747

AC:

10930

AN:

14628

East Asian (EAS)

AF:

0.842

AC:

26151

AN:

31068

South Asian (SAS)

AF:

0.742

AC:

26445

AN:

35654

European-Finnish (FIN)

AF:

0.829

AC:

31453

AN:

37922

Middle Eastern (MID)

AF:

0.736

AC:

2316

AN:

3146

European-Non Finnish (NFE)

AF:

0.779

AC:

422711

AN:

542686

Other (OTH)

AF:

0.783

AC:

27101

AN:

34612

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

6025

12050

18076

24101

30126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8404

16808

25212

33616

42020

<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:

0.798

AC:

121397

AN:

152186

Hom.:

48552

Cov.:

AF XY:

0.799

AC XY:

59396

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.835

AC:

34687

AN:

41540

American (AMR)

AF:

0.818

AC:

12501

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.749

AC:

2600

AN:

3472

East Asian (EAS)

AF:

0.808

AC:

4178

AN:

5172

South Asian (SAS)

AF:

0.731

AC:

3519

AN:

4816

European-Finnish (FIN)

AF:

0.823

AC:

8711

AN:

10584

Middle Eastern (MID)

AF:

0.728

AC:

214

AN:

294

European-Non Finnish (NFE)

AF:

0.774

AC:

52657

AN:

68000

Other (OTH)

AF:

0.792

AC:

1673

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1308

2616

3925

5233

6541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

878

1756

2634

3512

4390

<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:

0.783

Hom.:

26163

Bravo

AF:

0.801

Asia WGS

AF:

0.758

AC:

2634

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

(source)

DANN

Benign

0.46

PhyloP100

0.71

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over