Genetic Variant TNR:c.*3094G>A (chr1-175320263-C-T) – 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.*3094G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,072 control chromosomes in the GnomAD database, including 5,972 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 0.24 ( 5970 hom., cov: 32)

Exomes 𝑓: 0.13 ( 2 hom. )

Consequence

TNR
NM_003285.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.110

Publications

12 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:

ENSG00000260990 (HGNC:):

ENSG00000260990 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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.462 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.*3094G>A		3_prime_UTR	Exon 23 of 23	NP_003276.3
	TNR	NM_001328635.2		c.*3094G>A		3_prime_UTR	Exon 23 of 23	NP_001315564.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNR	ENST00000367674.7	TSL:5 MANE Select	c.*3094G>A	3_prime_UTR	Exon 23 of 23	ENSP00000356646.1	Q92752-1
TNR	ENST00000713954.1		c.*3094G>A	3_prime_UTR	Exon 20 of 20	ENSP00000519247.1	A0AAQ5BH57
ENSG00000260990	ENST00000569593.1	TSL:3	n.196-719C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.240

AC:

36369

AN:

151796

Hom.:

5945

Cov.:

show subpopulations

Gnomad AFR

AF:

0.468

Gnomad AMI

AF:

0.228

Gnomad AMR

AF:

0.166

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.0338

Gnomad SAS

AF:

0.0868

Gnomad FIN

AF:

0.177

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.213

GnomAD4 exome

AF:

0.127

AC:

AN:

158

Hom.:

Cov.:

AF XY:

0.157

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.108

AC:

AN:

130

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.409

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.240

AC:

36440

AN:

151914

Hom.:

5970

Cov.:

AF XY:

0.236

AC XY:

17501

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.468

AC:

19376

AN:

41404

American (AMR)

AF:

0.167

AC:

2543

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

492

AN:

3470

East Asian (EAS)

AF:

0.0342

AC:

177

AN:

5172

South Asian (SAS)

AF:

0.0859

AC:

413

AN:

4810

European-Finnish (FIN)

AF:

0.177

AC:

1873

AN:

10554

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.160

AC:

10868

AN:

67938

Other (OTH)

AF:

0.213

AC:

449

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1225

2449

3674

4898

6123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<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:

0.178

Hom.:

5404

Bravo

AF:

0.252

Asia WGS

AF:

0.0880

AC:

305

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

9.3

(source)

DANN

Benign

0.64

PhyloP100

0.11

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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